2851:. The advantage of compartmental over noncompartmental analysis is the ability to modify parameters and to extrapolate to novel situations. The disadvantage is the difficulty in developing and validating the proper model. Although compartment models have the potential to realistically model the situation within an organism, models inevitably make simplifying assumptions and will not be applicable in all situations. However complicated and precise a model may be, it still does not truly represent reality despite the effort involved in obtaining various distribution values for a drug. This is because the concept of distribution volume is a relative concept that is not a true reflection of reality. The choice of model therefore comes down to deciding which one offers the lowest margin of error for the drug involved.
3118:
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4396:
7084:
3302:
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31:
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4092:
that, if such changes are associated with clinically relevant and significant shifts in exposures that impact the therapeutic index, dosage can be appropriately modified. An advantage of population pharmacokinetic modelling is its ability to analyse sparse data sets (sometimes only one concentration measurement per patient is available).
3389:
administration of a drug provides the greatest possible bioavailability, and this method is considered to yield a bioavailability of 1 (or 100%). Bioavailability of other delivery methods is compared with that of intravenous injection (absolute bioavailability) or to a standard value related to other
3310:
Alpha phase: An initial phase of rapid decrease in plasma concentration. The decrease is primarily attributed to drug distribution from the central compartment (circulation) into the peripheral compartments (body tissues). This phase ends when a pseudo-equilibrium of drug concentration is established
3629:
Once a drug's bioavailability has been established it is possible to calculate the changes that need to be made to its dosage in order to reach the required blood plasma levels. Bioavailability is, therefore, a mathematical factor for each individual drug that influences the administered dose. It is
3078:
tissue) that present a real barrier to the distribution of drugs, that can be breached with greater or lesser ease depending on the drug's characteristics. If these relative conditions for the different tissue types are considered along with the rate of elimination, the organism can be considered to
927:
4091:
than they are in patients with normal kidney function receiving the same drug dosage. Population pharmacokinetics seeks to identify the measurable pathophysiologic factors and explain sources of variability that cause changes in the dose-concentration relationship and the extent of these changes so
4051:
is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank samples
243:
Some textbooks combine the first two phases as the drug is often administered in an active form, which means that there is no liberation phase. Others include a phase that combines distribution, metabolism and excretion into a disposition phase. Other authors include the drug's toxicological aspect
2826:
in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer time points are, the closer the trapezoids reflect the actual shape of the concentration-time curve. The number of time points available in order to perform a successful NCA
4367:
in a number of patients. However, it was then realized that it was possible to individualize a patient's dose of ciclosporin by analysing the patients plasmatic concentrations (pharmacokinetic monitoring). This practice has allowed this drug to be used again and has facilitated a great number of
2813:
Noncompartmental methods estimate PK parameters directly from a table of concentration-time measurements. Noncompartmental methods are versatile in that they do not assume any specific model and generally produce accurate results acceptable for bioequivalence studies. Total drug exposure is most
3125:
In the real world, each tissue will have its own distribution characteristics and none of them will be strictly linear. The two-compartment model may not be applicable in situations where some of the enzymes responsible for metabolizing the drug become saturated, or where an active elimination
4086:
is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest. Certain patient demographic, pathophysiological, and therapeutical features, such as body weight,
3329:: When the dose of a drug whose elimination depends on biotransformation is increased above a certain threshold the enzymes responsible for its metabolism become saturated. The drug's plasma concentration will then increase disproportionately and its elimination will no longer be constant.
2827:
analysis should be enough to cover the absorption, distribution and elimination phase to accurately characterize the drug. Beyond AUC exposure measures, parameters such as Cmax (maximum concentration), Tmax (time to maximum concentration), CL and Vd can also be reported using NCA methods.
4087:
excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships and can explain variability in exposures. For example, steady-state concentrations of drugs eliminated mostly by the kidney are usually greater in patients with
4351:
Clinical pharmacokinetics (arising from the clinical use of population pharmacokinetics) is the direct application to a therapeutic situation of knowledge regarding a drug's pharmacokinetics and the characteristics of a population that a patient belongs to (or can be ascribed to).
3102:
are organs with a good blood supply. However, in some situations it may be that elimination occurs in the peripheral compartment or even in both. This can mean that there are three possible variations in the two compartment model, which still do not cover all possibilities.
2875:
concentrations of the drug are the only information needed to determine the drug's concentration in other fluids and tissues. For example, the concentration in other areas may be approximately related by known, constant factors to the blood plasma concentration.
93:. Pharmacokinetics is based on mathematical modeling that places great emphasis on the relationship between drug plasma concentration and the time elapsed since the drug's administration. Pharmacokinetics is the study of how an organism affects the drug, whereas
5141:
Li, Xue; Martinez-Lozano Sinues, Pablo; Dallmann, Robert; Bregy, Lukas; Hollmén, Maija; Proulx, Steven; Brown, Steven A.; Detmar, Michael; Kohler, Malcolm; Zenobi, Renato (2015-06-26). "Drug
Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath".
2638:
3624:
2484:
2748:
Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. Pharmacokinetic modelling may be performed either by noncompartmental or
2769:
when designing generic drugs) or in the clinical application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in
4038:
because of the complex nature of the matrix (often plasma or urine) and the need for high sensitivity to observe concentrations after a low dose and a long time period. The most common instrumentation used in this application is
3298:
are removed from the plasma through two primary mechanisms: (1) Distribution to body tissues and (2) metabolism + excretion of the drugs. The resulting decrease of the drug's plasma concentration follows a biphasic pattern (see
709:
2712:
4371:
Clinical monitoring is usually carried out by determination of plasma concentrations as this data is usually the easiest to obtain and the most reliable. The main reasons for determining a drug's plasma concentration include:
1850:
4052:
taken before administration are important in determining background and ensuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is common to use
34:
A graph depicting a typical time course of drug plasma concentration over 96 hours, with oral administrations every 24 hours. The main pharmacokinetic metrics are annotated. Steady state is reached after about 5 × 12 = 60
3929:
at which there is an equilibrium between its ionized and non-ionized molecules), it is possible to calculate the non-ionized concentration of the drug and therefore the concentration that will be subject to absorption:
2731:
with its elimination. In practice, it is generally considered that once regular dosing of a drug is started, steady state is reached after 3 to 5 times its half-life. In steady state and in linear pharmacokinetics,
3060:
3505:
4572:
3989:
3258:
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2835:
Compartment models methods estimate the concentration-time graph by modeling it as a system of differential equations. These models are based on a consideration of an organism as a number of related
1081:
1569:
3843:
2227:
2098:
151:
A number of phases occur once the drug enters into contact with the organism, these are described using the acronym ADME (or LADME if liberation is included as a separate step from absorption):
2176:
2053:
1692:
1436:
2941:
2301:
663:
984:
2554:
1313:
1030:
2145:
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The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason, in order to fully comprehend the
5076:
Covey TR, Crowther JB, Dewey EA, Henion JD (February 1985). "Thermospray liquid chromatography/mass spectrometry determination of drugs and their metabolites in biological fluids".
3780:
1965:
5323:
3314:
Beta phase: A phase of gradual decrease in plasma concentration after the alpha phase. The decrease is primarily attributed to drug elimination, that is, metabolism and excretion.
1620:
1364:
1238:
2972:
1180:
3363:
It can therefore be seen that non-linearity can occur because of reasons that affect the entire pharmacokinetic sequence: absorption, distribution, metabolism and elimination.
1766:
1510:
1278:
703:
530:
3734:
These concepts, which are discussed in detail in their respective titled articles, can be mathematically quantified and integrated to obtain an overall mathematical equation:
1928:
2022:
3670:
580:
490:
384:
5405:
1891:
1733:
1643:
1477:
1387:
1145:
1122:
603:
444:
4691:
3513:
3094:
Two-compartment models vary depending on which compartment elimination occurs in. The most common situation is that elimination occurs in the central compartment as the
113:
2406:
4541:
3923:
3889:
2527:
421:
2998:
3869:
2548:
2261:
5361:
Jager T, Albert C, Preuss TG, Ashauer R (April 2011). "General unified threshold model of survival--a toxicokinetic-toxicodynamic framework for ecotoxicology".
4446:
2397:
355:
5041:
Covey TR, Lee ED, Henion JD (October 1986). "High-speed liquid chromatography/tandem mass spectrometry for the determination of drugs in biological samples".
3074:, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (such as the
922:{\displaystyle C_{min}={\frac {SFDk_{a}}{V_{d}(k_{a}-k)}}\times \{{\frac {e^{-k_{e}\tau }}{1-e^{-k_{e}\tau }}}-{\frac {e^{-k_{a}\tau }}{1-e^{-k_{a}\tau }}}\}}
2644:
5187:
Sheiner LB, Rosenberg B, Marathe VV (October 1977). "Estimation of population characteristics of pharmacokinetic parameters from routine clinical data".
3694:
Therefore, if a drug has a bioavailability of 0.8 (or 80%) and it is administered in a dose of 100 mg, the equation will demonstrate the following:
4363:
to facilitate organ transplant. The drug's therapeutic properties were initially demonstrated, but it was almost never used after it was found to cause
4998:
Hsieh Y, Korfmacher WA (June 2006). "Increasing speed and throughput when using HPLC-MS/MS systems for drug metabolism and pharmacokinetic screening".
3385:
At a practical level, a drug's bioavailability can be defined as the proportion of the drug that reaches its site of action. From this perspective the
3087:
made up of organs with a lower blood flow. Other tissues, such as the brain, can occupy a variable position depending on a drug's ability to cross the
1772:
5810:
7067:
6824:
5613:
4848:
4692:"Collection of terms, symbols, equations, and explanations of common pharmacokinetic and pharmacodynamic parameters and some statistical functions"
5889:
4900:
Baaske P, Wienken CJ, Reineck P, Duhr S, Braun D (March 2010). "Optical thermophoresis for quantifying the buffer dependence of aptamer binding".
4040:
3705:
That is the 100 mg administered represents a blood plasma concentration of 80 mg that has the capacity to have a pharmaceutical effect.
1974:
5936:
3282:; the relationships between the factors can then be found by calculating the dimensions of different areas under the curve. The models used in
5113:"ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals"
6028:
5993:
5508:
3003:
1095:
The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration in plasma to drug amount in the body).
2757:
provide the best approximations to reality; however, the complexity involved in adding parameters with that modelling approach means that
4429:
is the branch of science that deals with the nature, effects, and interactions of substances that are harmful to the environment such as
3396:
65:
dedicated to describing how the body affects a specific substance after administration. The substances of interest include any chemical
4437:
harmful substances. Ecotoxicology is studied in pharmacokinetics due to the substances responsible for harming the environment such as
6764:
6722:
3936:
3630:
possible to calculate the amount of a drug in the blood plasma that has a real potential to bring about its effect using the formula:
3150:
2307:
5763:
5534:
5349:
5112:
4887:
4860:
4811:
4639:
4072:
5666:
4018:
are necessary to construct a concentration-time profile. Chemical techniques are employed to measure the concentration of drugs in
2867:
The simplest PK compartmental model is the one-compartmental PK model. This models an organism as one homogenous compartment. This
295:, simply replace 'mol' with 'g' and 'M' with 'g/L'. Similarly, other units in the table may be expressed in units of an equivalent
3352:. As larger doses of these pharmaceuticals are administered the plasma concentrations of the unmetabolized drug increases and the
263:
of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as
7042:
6712:
5609:
5589:
5409:
2883:, where the elimination of the drug is directly proportional to the drug's concentration in the organism. This is often called
2801:, absorption capacity and distribution in the organism. A variety of analysis techniques may be used to develop models, such as
7171:
7062:
6652:
6145:
4698:
6180:
1036:
6707:
6403:
6314:
3895:
2750:
3994:
When two drugs have the same bioavailability, they are said to be biological equivalents or bioequivalents. This concept of
3287:
4697:. Arbeitsgemeinschaft für Angewandte Humanpharmakologie (AGAH) (Association for Applied Human Pharmacology). Archived from
1516:
6632:
6257:
3795:
3680:
283:
The following are the most commonly measured pharmacokinetic metrics: The units of the dose in the table are expressed in
3144:
the former will be described by an equation that takes into account all the tissues that act in different ways, that is:
2789:, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its
2182:
2059:
89:
and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely
6185:
5575:
127:
Process of the uptake of drugs by the body, the biotransformation they undergo, the distribution of the drugs and their
7037:
6375:
4506:
4476:
185:
5516:
5512:
5496:
3356:
increases. It is therefore necessary to adjust the dose or other treatment parameters when a high dosage is required.
2843:
are in use. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as
4826:"Phase I Pharmacokinetics of Liposomal Amikacin (MiKasome) in Human Subjects: Dose Dependence and Urinary Clearance"
2151:
2028:
1649:
1393:
6110:
5929:
4441:
can get into the bodies of living organisms. The health effects of these chemicals is thus subject to research and
2790:
2633:{\displaystyle 100{\frac {C_{{\text{max}},{\text{ss}}}-C_{{\text{min}},{\text{ss}}}}{C_{{\text{av}},{\text{ss}}}}}}
2267:
253:
223:
164:
5593:
3359:
The kidneys can also establish active elimination mechanisms for some drugs, independent of plasma concentrations.
2890:
631:
7161:
6622:
6370:
6364:
5119:
4450:
4023:
1701:
952:
174:
155:
2765:
are the most-frequently used. The model outputs for a drug can be used in industry (for example, in calculating
7032:
6873:
6687:
6389:
5901:
5877:
5567:
4048:
4044:
2778:
1445:
1284:
990:
5718:
3088:
2109:
204:(or biotransformation, or inactivation) – the chemical reactions of the drug and irreversible breakdown into
7014:
6438:
6200:
6195:
6105:
6023:
3720:
3375:
Different forms of tablets, which will have different pharmacokinetic behaviours after their administration.
3267:
with a number of curves that express complicated equations in order to obtain an overall curve. A number of
3112:
3083:
that has a more rapid distribution, comprising organs and systems with a well-developed blood supply; and a
2840:
2754:
217:
3740:
1934:
131:
in the tissues, and the elimination of the drugs and their metabolites from the body over a period of time.
6757:
6574:
6335:
6310:
6245:
6134:
6018:
4360:
4068:
3127:
1090:
5230:
Sheiner LB, Beal S, Rosenberg B, Marathe VV (September 1979). "Forecasting individual pharmacokinetics".
1588:
1332:
1203:
6989:
6974:
6682:
6474:
6276:
5953:
5922:
5905:
2950:
2819:
1151:
5431:
4026:
can be used to quantify how the biological matrix/liquid affects the affinity of a drug to its target.
1739:
1483:
1244:
669:
496:
1897:
7057:
6994:
6888:
6797:
6717:
6579:
6489:
6330:
6210:
5978:
5909:
5868:
Global centres with the highest profiles for providing in-depth training include the
Universities of
5643:
5370:
4962:
4491:
4481:
4454:
3353:
2880:
2802:
2493:
2233:
1988:
1578:
1322:
396:
5745:
3636:
3619:{\displaystyle {\mathit {B}}_{R}={\frac {_{A}\cdot {\text{dose}}_{B}}{_{B}\cdot {\text{dose}}_{A}}}}
3126:
mechanism is present that is independent of the drug's plasma concentration. If we label the drug's
558:
468:
361:
7004:
6936:
6919:
6898:
6819:
6792:
6627:
6515:
6484:
6130:
6090:
6013:
4655:
Ruiz-Garcia A, Bermejo M, Moss A, Casabo VG (February 2008). "Pharmacokinetics in drug discovery".
4063:
There is currently considerable interest in the use of very high sensitivity mass spectrometry for
3712:
3386:
3295:
2944:
2782:
2771:
2728:
1869:
616:
542:
456:
330:
292:
70:
4825:
4022:, most often plasma. Proper bioanalytical methods should be selective and sensitive. For example,
3117:
1711:
1626:
1455:
1370:
1128:
1100:
586:
427:
6999:
6962:
6931:
6597:
6547:
6448:
6261:
6240:
6140:
6061:
5973:
5897:
5873:
5869:
5738:
5255:
5212:
5023:
4612:
4268:
4075:(SESI-MS) can be used in drug monitoring, presenting the advantage of avoiding animal sacrifice.
4057:
2479:{\displaystyle {\frac {AUC_{\text{po}}\cdot D_{\text{iv}}}{AUC_{\text{iv}}\cdot D_{\text{po}}}}}
1327:
The time required for 50% of a given dose of drug to be absorbed into the systemic circulation.
5710:
4060:
since the response of most mass spectrometers is not linear across large concentration ranges.
3322:
A drug's characteristics make a clear distinction between tissues with high and low blood flow.
7166:
7138:
7087:
7052:
6979:
6957:
6893:
6809:
6750:
6592:
6453:
6443:
6271:
6265:
6100:
5893:
5881:
5386:
5345:
5304:
5247:
5204:
5169:
5093:
5058:
5015:
4980:
4917:
4883:
4856:
4807:
4763:
4731:
4672:
4635:
4546:
4035:
4019:
3337:
2887:, as the change in concentration over time can be expressed as a linear differential equation
2859:
2844:
193:– the dispersion or dissemination of substances throughout the fluids and tissues of the body.
54:
7128:
7120:
7047:
7022:
6984:
6861:
6849:
6637:
6525:
6520:
6320:
6076:
6056:
6038:
5885:
5852:
5647:
5378:
5294:
5286:
5239:
5196:
5159:
5151:
5085:
5050:
5007:
4970:
4909:
4664:
4602:
4511:
4501:
4471:
3336:: Some drugs have the capacity to inhibit or stimulate their own metabolism, in negative or
3333:
3268:
2815:
94:
5798:
3901:
3874:
2503:
406:
6967:
6941:
6854:
6677:
6552:
6380:
6340:
6325:
6033:
5983:
5730:
5682:
5563:
4521:
4496:
4486:
3380:
3278:
The graph for the non-linear relationship between the various factors is represented by a
2794:
2372:
272:
213:
182:– the process of a drug entering into systemic circulation from the site of administration
17:
3275:
models) rely on the use of physiological information to ease development and validation.
2977:
1583:
The time required for the concentration of the drug to reach half of its original value.
5374:
4966:
3851:
2533:
2243:
7133:
7108:
7027:
6926:
6667:
6647:
6566:
6408:
6150:
6095:
5299:
5274:
4551:
4531:
4442:
4364:
4291:
4260:
4244:
4088:
3995:
2848:
2766:
2382:
1450:
The rate at which a drug enters into the body for oral and other extravascular routes.
340:
102:
5741:
5726:
5674:
5605:
4824:
Gill SC, Moon-Mcdermott L, Hunt TL, Deresinski S, Blaschke T, Sandhaus RA (Sep 1999).
4395:
7155:
7124:
6883:
6878:
6672:
6159:
6066:
4536:
4430:
4426:
4211:
4163:
4148:
4143:
4106:
4053:
1859:
1189:
268:
252:. The two phases of metabolism and excretion can be grouped together under the title
78:
43:
5455:
5259:
5216:
5027:
4616:
2707:{\displaystyle C_{{\text{av}},{\text{ss}}}={\frac {AUC_{\tau ,{\text{ss}}}}{\tau }}}
6840:
6642:
6602:
6503:
6427:
6305:
5988:
5945:
5678:
4286:
4277:
4158:
3999:
3371:
3326:
2872:
1195:
944:
623:
288:
106:
62:
4376:
Narrow therapeutic range (difference between toxic and therapeutic concentrations)
3301:
5794:
5341:
3998:
is important because it is currently used as a yardstick in the authorization of
231:– the removal of the substance or metabolites from the body. In rare cases, some
6787:
6727:
6214:
6190:
5782:
5722:
5670:
5597:
4576:. Philadelphia, PA: Elsevier Health Sciences. Retrieved December 11, 2008, from
4516:
4458:
4356:
4323:
4191:
4153:
4064:
4015:
3341:
3271:
have been developed to plot these equations. The most complex PK models (called
1845:{\displaystyle {\frac {\ln(2)}{t_{{\frac {1}{2}}b}}}={\frac {CL}{V_{\text{d}}}}}
284:
236:
128:
97:(PD) is the study of how the drug affects the organism. Both together influence
30:
5164:
5011:
4755:
4723:
6914:
6866:
6804:
6607:
6539:
6431:
6206:
4951:"Protein-binding assays in biological liquids using microscale thermophoresis"
4577:
4335:
4296:
4252:
4235:
4225:
4220:
4206:
4196:
4126:
3728:
3345:
2798:
2785:. The use of these models allows an understanding of the characteristics of a
205:
196:
86:
66:
4878:
Michael E. Winter, Mary Anne Koda-Kimple, Lloyd Y. Young, Emilio Pol
Yanguas
6385:
5824:
4929:
4607:
4590:
4438:
4434:
4341:
4329:
4314:
4309:
4304:
4201:
4182:
4168:
4138:
3708:
This concept depends on a series of factors inherent to each drug, such as:
3349:
3121:
Graphs for absorption and elimination for a non-linear pharmacokinetic model
296:
264:
90:
82:
74:
7142:
5571:
5408:. Swiss Federal Institute of Aquatic Science and Technology. Archived from
5390:
5308:
5173:
5155:
5019:
4984:
4921:
4913:
4767:
4735:
4676:
5243:
5097:
5062:
1983:
of the concentration-time curve (after a single dose or in steady state).
626:) concentration that a drug reaches before the next dose is administered.
271:
and the way that substances can cross them, or the characteristics of the
6814:
6773:
6507:
6479:
6466:
6235:
6155:
5640:
SBPKPD.org (Systems
Biology Driven Pharmacokinetics and Pharmacodynamics)
5251:
5208:
4526:
4230:
2786:
1980:
5290:
5089:
5054:
4853:
Pharmacokinetic/pharmacodynamic data analysis: concepts and applications
2727:
refers to the situation where the overall intake of a drug is fairly in
5968:
5759:
5200:
5111:
Committee for
Medicinal Products for Human Use (CHMP) (December 2009).
4975:
4950:
4786:
4591:"Glossary of terms used in toxicokinetics (IUPAC Recommendations 2003)"
4177:
3891:
is the rate at which the absorbed drug reaches the circulatory system.
3099:
2879:
In this one-compartment model, the most common model of elimination is
943:
The average plasma concentration of a drug over the dosing interval in
5786:
5700:
5627:
5382:
4668:
291:(M). To express the metrics of the table in units of mass, instead of
5848:
5790:
5686:
3055:{\displaystyle C=C_{\text{initial}}\times e^{-k_{\text{el}}\times t}}
209:
98:
5275:"Recommended reading in population pharmacokinetic pharmacodynamics"
5802:
5767:
5515:
external links, and converting useful links where appropriate into
4949:
Wienken CJ, Baaske P, Rothbauer U, Braun D, Duhr S (October 2010).
3390:
delivery methods in a particular study (relative bioavailability).
2498:
Peak–trough fluctuation within one dosing interval at steady state.
5651:
3500:{\displaystyle B_{A}={\frac {_{P}\cdot D_{IV}}{_{IV}\cdot D_{P}}}}
3300:
3279:
3095:
3075:
3071:
232:
168:
29:
5324:"Mecanismos de nefrotoxicidad por ciclosporina A a nivel celular"
2822:) the most common method. Due to the dependence on the length of
6360:
6253:
6249:
6051:
5856:
5635:
5585:
4573:
Mosby's
Dictionary of Medicine, Nursing & Health Professions
3984:{\displaystyle \mathrm {pH} =\mathrm {pKa} +\log {\frac {B}{A}}}
3272:
3253:{\displaystyle Vd_{F}=Vd_{T1}+Vd_{T2}+Vd_{T3}+\cdots +Vd_{Tn}\,}
2814:
often estimated by area under the curve (AUC) methods, with the
937:
146:
6746:
5918:
5914:
5559:
5406:"Toxicokinetic-Toxicodynamic Models – Ecotoxicology and Models"
3290:. A reaction's factors of non-linearity include the following:
2358:{\displaystyle V_{\text{d}}\cdot k_{\text{e}}={\frac {D}{AUC}}}
5714:
5479:
5122:, Evaluation of Medicines for Human Use. EMA/CPMP/ICH/286/1995
4390:
463:
The peak plasma concentration of a drug after administration.
5344:(in Spanish). Published by Elsevier España, 2003; page 159.
3520:
6742:
5581:
3926:
163:– the process of the active ingredient separating from its
4634:(in German). Landsberg, München: Ecomed. pp. 99–131.
3317:
Additional phases (gamma, delta, etc.) are sometimes seen.
3079:
be acting like two compartments: one that we can call the
5774:
5734:
5658:
5639:
5631:
5601:
5828:
5806:
5778:
5662:
1076:{\displaystyle {\frac {AUC_{\tau ,{\text{ss}}}}{\tau }}}
5504:
5499:
may not follow
Knowledge (XXG)'s policies or guidelines
5322:
O'Valle, F.; García del Moral, R.; Andujar, M. (1995).
4461:
4407:
2238:
The volume of plasma cleared of the drug per unit time.
4101:
Drugs where pharmacokinetic monitoring is recommended
4067:
studies, which are seen as a promising alternative to
2893:
4589:
Nordberg M, Duffus J, Templeton DM (1 January 2004).
3939:
3904:
3877:
3854:
3798:
3743:
3639:
3516:
3399:
3153:
3006:
2980:
2953:
2863:
Graph representing the monocompartmental action model
2647:
2557:
2536:
2506:
2409:
2385:
2310:
2270:
2246:
2185:
2154:
2112:
2062:
2031:
1991:
1937:
1900:
1872:
1775:
1742:
1714:
1652:
1629:
1591:
1564:{\displaystyle {\frac {\ln(2)}{t_{{\frac {1}{2}}a}}}}
1519:
1486:
1458:
1396:
1373:
1335:
1287:
1247:
1206:
1154:
1131:
1103:
1039:
993:
955:
712:
672:
634:
589:
561:
499:
471:
430:
409:
364:
343:
5844:
5706:
4445:
by government or international agencies such as the
3838:{\displaystyle Va={\frac {Da\cdot B\cdot Q}{\tau }}}
7013:
6950:
6907:
6833:
6780:
6700:
6660:
6616:
6565:
6538:
6502:
6465:
6426:
6417:
6353:
6298:
6289:
6228:
6173:
6122:
6084:
6075:
6006:
5961:
5952:
2222:{\displaystyle \int _{t}^{t+\tau }C\,\mathrm {d} t}
2093:{\displaystyle \int _{0}^{\infty }C\,\mathrm {d} t}
5342:Manual de farmacia clínica y Atención Farmacéutica
4690:AGAH working group PHARMACOKINETICS (2004-02-16).
3983:
3917:
3883:
3863:
3837:
3774:
3664:
3618:
3499:
3305:Plasma drug concentration vs time after an IV dose
3252:
3054:
2992:
2966:
2935:
2706:
2632:
2542:
2521:
2478:
2391:
2357:
2295:
2255:
2221:
2170:
2139:
2092:
2047:
2016:
1959:
1922:
1885:
1844:
1760:
1727:
1706:The rate at which a drug is removed from the body.
1686:
1637:
1614:
1563:
1504:
1471:
1430:
1381:
1358:
1307:
1272:
1232:
1174:
1139:
1116:
1075:
1024:
978:
921:
697:
657:
597:
574:
524:
484:
438:
415:
378:
349:
1864:Rate of infusion required to balance elimination.
5189:Journal of Pharmacokinetics and Biopharmaceutics
3311:between the central and peripheral compartments.
3091:that separates the organ from the blood supply.
401:Time interval between drug dose administrations.
4830:Abstr Intersci Conf Antimicrob Agents Chemother
4787:"Pharmacokinetics – Online content for student"
4762:, Treasure Island (FL): StatPearls Publishing,
4730:, Treasure Island (FL): StatPearls Publishing,
4542:Physiologically based pharmacokinetic modelling
118:
2377:The systemically available fraction of a drug.
2171:{\displaystyle \mathrm {M} \cdot \mathrm {s} }
2048:{\displaystyle \mathrm {M} \cdot \mathrm {s} }
1687:{\displaystyle {\frac {\ln(2)}{k_{\text{e}}}}}
1431:{\displaystyle {\frac {\ln(2)}{k_{\text{a}}}}}
6758:
5930:
4632:Synopsis der Biopharmazie und Pharmakokinetik
2936:{\textstyle {\frac {dC}{dt}}=-k_{\text{el}}C}
2296:{\displaystyle \mathrm {m} ^{3}/\mathrm {s} }
8:
4754:Hallare, Jericho; Gerriets, Valerie (2023),
4722:Hallare, Jericho; Gerriets, Valerie (2021),
916:
794:
658:{\displaystyle C_{{\text{min}},{\text{ss}}}}
4630:Koch HP, Ritschel WA (1986). "Liberation".
4578:http://www.credoreference.com/entry/6686418
3137:and its volume of distribution in a tissue
979:{\displaystyle C_{{\text{av}},{\text{ss}}}}
6765:
6751:
6743:
6697:
6657:
6562:
6535:
6499:
6462:
6423:
6350:
6295:
6225:
6170:
6119:
6081:
6003:
5958:
5937:
5923:
5915:
4099:
7132:
7109:"Research priorities in pharmacokinetics"
5535:Learn how and when to remove this message
5298:
5163:
4974:
4882:Ediciones Díaz de Santos, 1994 pgs. 8–14
4874:
4872:
4798:
4796:
4606:
4455:How long these chemicals stay in the body
4355:An example is the relaunch of the use of
3971:
3951:
3940:
3938:
3914:
3903:
3876:
3871:is the drug's rate of administration and
3853:
3808:
3797:
3771:
3742:
3661:
3638:
3607:
3602:
3592:
3568:
3563:
3553:
3534:
3525:
3519:
3518:
3515:
3488:
3472:
3445:
3432:
3413:
3404:
3398:
3249:
3240:
3215:
3196:
3177:
3161:
3152:
3038:
3030:
3017:
3005:
2979:
2958:
2952:
2924:
2894:
2892:
2691:
2684:
2671:
2661:
2653:
2652:
2646:
2621:
2613:
2612:
2600:
2592:
2591:
2577:
2569:
2568:
2561:
2556:
2535:
2505:
2467:
2454:
2436:
2423:
2410:
2408:
2384:
2337:
2328:
2315:
2309:
2288:
2283:
2277:
2272:
2269:
2245:
2211:
2210:
2195:
2190:
2184:
2163:
2155:
2153:
2130:
2123:
2111:
2082:
2081:
2072:
2067:
2061:
2040:
2032:
2030:
2002:
1990:
1942:
1936:
1911:
1901:
1899:
1877:
1871:
1834:
1820:
1800:
1799:
1776:
1774:
1749:
1744:
1741:
1719:
1713:
1676:
1653:
1651:
1630:
1628:
1597:
1596:
1590:
1544:
1543:
1520:
1518:
1493:
1488:
1485:
1463:
1457:
1420:
1397:
1395:
1374:
1372:
1341:
1340:
1334:
1308:{\displaystyle {\frac {D}{V_{\text{d}}}}}
1297:
1288:
1286:
1261:
1248:
1246:
1224:
1211:
1205:
1164:
1155:
1153:
1132:
1130:
1108:
1102:
1060:
1053:
1040:
1038:
1025:{\displaystyle \mathrm {h\times mmol/L} }
1013:
994:
992:
969:
961:
960:
954:
902:
894:
872:
864:
858:
841:
833:
811:
803:
797:
773:
760:
748:
732:
717:
711:
686:
673:
671:
648:
640:
639:
633:
590:
588:
566:
560:
513:
500:
498:
476:
470:
431:
429:
408:
365:
363:
342:
267:, the characteristics of the appropriate
7113:British Journal of Clinical Pharmacology
6825:Separation of prescribing and dispensing
5762:, ADAPT, S-ADAPT / SADAPT-TRAN, Boomer,
4034:Pharmacokinetics is often studied using
3370:
3116:
2858:
301:
7099:
5908:, Monash University, and University of
5144:Angewandte Chemie International Edition
4855:. Apotekarsocieteten. pp. 527–36.
4563:
3294:Multiphasic absorption: Drugs injected
2140:{\displaystyle AUC_{\tau ,{\text{ss}}}}
85:, etc. It attempts to analyze chemical
5363:Environmental Science & Technology
5232:Clinical Pharmacology and Therapeutics
4849:"PK24 – Non-linear kinetics – flow II"
3775:{\displaystyle De=Q\cdot Da\cdot B\,}
3000:, the equation can be solved to give
1960:{\displaystyle C_{\text{ss}}\cdot CL}
7:
4056:with more complex functions such as
1194:Amount of drug in a given volume of
134:Study of more such related processes
4045:triple quadrupole mass spectrometer
3070:Not all body tissues have the same
1615:{\displaystyle t_{{\frac {1}{2}}b}}
1359:{\displaystyle t_{{\frac {1}{2}}a}}
1233:{\displaystyle C_{0},C_{\text{ss}}}
6723:Minimum bactericidal concentration
4657:Journal of Pharmaceutical Sciences
3958:
3955:
3952:
3944:
3941:
2967:{\displaystyle C_{\text{initial}}}
2777:Models generally take the form of
2537:
2507:
2289:
2273:
2212:
2164:
2156:
2083:
2073:
2041:
2033:
2009:
1916:
1908:
1905:
1902:
1745:
1631:
1489:
1375:
1266:
1258:
1255:
1252:
1249:
1175:{\displaystyle {\frac {D}{C_{0}}}}
1133:
1018:
1010:
1007:
1004:
1001:
995:
691:
683:
680:
677:
674:
591:
518:
510:
507:
504:
501:
432:
372:
369:
366:
25:
5818:Therapeutic drug monitoring (TDM)
4073:Secondary electrospray ionization
1761:{\displaystyle \mathrm {h} ^{-1}}
1505:{\displaystyle \mathrm {h} ^{-1}}
1273:{\displaystyle \mathrm {mmol/L} }
698:{\displaystyle \mathrm {mmol/L} }
525:{\displaystyle \mathrm {mmol/L} }
53:"moving, putting in motion"; see
7125:10.1111/j.1365-2125.2012.04238.x
7083:
7082:
7043:List of pharmaceutical companies
6713:Minimum inhibitory concentration
5839:All model based software above.
5484:
4847:Weiner D, Gabrielsson J (2000).
4394:
1923:{\displaystyle \mathrm {mol/h} }
7063:Pharmacies in the United States
6653:WHO list of essential medicines
6146:Non-specific effect of vaccines
2017:{\displaystyle AUC_{0-\infty }}
6708:Antimicrobial pharmacodynamics
5330:(in Spanish). 15 Supplement 1.
4880:Farmacocinética clínica básica
4802:Milo Gibaldi, Donald Perrier.
3896:Henderson-Hasselbalch equation
3665:{\displaystyle De=B\cdot Da\,}
3589:
3576:
3550:
3537:
3469:
3456:
3429:
3416:
2839:. Both single compartment and
1791:
1785:
1668:
1662:
1535:
1529:
1412:
1406:
785:
766:
575:{\displaystyle t_{\text{max}}}
485:{\displaystyle C_{\text{max}}}
379:{\displaystyle \mathrm {mol} }
1:
6633:Functional analog (chemistry)
5432:"Chemicals and Toxics Topics"
4570:Pharmacokinetics. (2006). In
2947:resulting in a concentration
2943:. Assuming a single IV bolus
1886:{\displaystyle k_{\text{in}}}
549:Minimum time taken to reach C
6186:Hill equation (biochemistry)
4890:, 9788479781477 (in Spanish)
1728:{\displaystyle k_{\text{e}}}
1638:{\displaystyle \mathrm {h} }
1579:Elimination half-life
1472:{\displaystyle k_{\text{a}}}
1382:{\displaystyle \mathrm {h} }
1140:{\displaystyle \mathrm {L} }
1117:{\displaystyle V_{\text{d}}}
938:Average plasma concentration
617:Minimum plasma concentration
598:{\displaystyle \mathrm {h} }
439:{\displaystyle \mathrm {h} }
335:Amount of drug administered.
57:), sometimes abbreviated as
7038:Pharmacy benefit management
5652:PharmaCalc and PharmaCalcCL
4507:Idiosyncratic drug reaction
4477:Blood alcohol concentration
4084:Population pharmacokinetics
4079:Population pharmacokinetics
4071:. Recent studies show that
3284:non-linear pharmacokinetics
458:Maximum serum concentration
235:irreversibly accumulate in
7188:
6701:Antimicrobial pharmacology
6181:Dose–response relationship
6111:Desensitization (medicine)
5430:US EPA, OMS (2016-11-17).
5273:Bonate PL (October 2005).
5012:10.2174/138920006777697963
4595:Pure and Applied Chemistry
3378:
3340:reactions. As occurs with
3110:
2791:acid dissociation constant
2781:that have a corresponding
275:that inactivate the drug.
165:pharmaceutical formulation
144:
18:Steady-state concentration
7078:
6623:Coinduction (anesthetics)
5340:Joaquín Herrera Carranza
5120:European Medicines Agency
4930:"A hot road to new drugs"
4836:: 33 (abstract no. 1195).
4806:Reverté 1982 pages 1–10.
4096:Clinical pharmacokinetics
4024:microscale thermophoresis
3898:, and knowing the drug's
3288:Michaelis–Menten kinetics
2809:Noncompartmental analysis
2101:
1978:
1973:
1702:Elimination rate constant
7033:Investigational New Drug
6874:Pharmaceutical chemistry
6820:Pharmacological activity
6688:Multiple drug resistance
6661:Tolerance and resistance
6029:Physiological antagonist
4049:Tandem mass spectrometry
3107:Multi-compartment models
2855:Single-compartment model
2841:multi-compartment models
2783:graphical representation
2763:two compartmental models
2759:monocompartmental models
2755:Multi-compartment models
1446:Absorption rate constant
303:Pharmacokinetic metrics
91:eliminated from the body
7107:Tucker GT (June 2012).
7015:Pharmaceutical industry
6834:Pharmaceutical sciences
6439:Neuropsychopharmacology
6201:Cheng-Prussoff Equation
6196:Del Castillo Katz model
6123:Other effects of ligand
6106:Receptor (biochemistry)
6024:Irreversible antagonist
5000:Current Drug Metabolism
4608:10.1351/pac200476051033
3721:Route of administration
3691:the administered dose.
3265:multi-compartment model
3113:Multi-compartment model
2885:linear pharmacokinetics
2869:monocompartmental model
218:glucuronosyltransferase
7172:Life sciences industry
6575:Classical pharmacology
6336:Plasma protein binding
6311:Volume of distribution
6019:Competitive antagonist
5156:10.1002/anie.201503312
4914:10.1002/anie.200903998
4069:animal experimentation
3985:
3919:
3885:
3865:
3839:
3789:is the drug's purity.
3776:
3701:= 0.8 × 100 mg = 80 mg
3666:
3620:
3501:
3376:
3306:
3254:
3128:volume of distribution
3122:
3085:peripheral compartment
3056:
2994:
2968:
2937:
2864:
2831:Compartmental analysis
2708:
2634:
2544:
2523:
2480:
2393:
2359:
2297:
2257:
2223:
2172:
2141:
2094:
2049:
2018:
1961:
1924:
1887:
1846:
1762:
1729:
1688:
1639:
1616:
1565:
1506:
1473:
1432:
1383:
1360:
1309:
1274:
1234:
1176:
1141:
1118:
1091:Volume of distribution
1077:
1026:
980:
923:
699:
659:
599:
576:
526:
486:
440:
417:
380:
351:
137:
36:
27:Branch of pharmacology
6990:Pharmacist prescriber
6975:Consultant pharmacist
6683:Antibiotic resistance
6475:Clinical pharmacology
5994:Physiological agonist
5954:Ligand (biochemistry)
5694:Physiologically based
5244:10.1002/cpt1979263294
4955:Nature Communications
4016:Bioanalytical methods
4011:Bioanalytical methods
3986:
3920:
3918:{\displaystyle pKa\,}
3886:
3884:{\displaystyle \tau }
3866:
3840:
3777:
3667:
3621:
3502:
3374:
3354:elimination half-life
3304:
3286:are largely based on
3255:
3120:
3111:Further information:
3066:Two-compartment model
3057:
2995:
2969:
2938:
2862:
2820:numerical integration
2779:mathematical formulas
2723:In pharmacokinetics,
2709:
2635:
2545:
2524:
2522:{\displaystyle \%PTF}
2481:
2394:
2360:
2298:
2258:
2224:
2173:
2142:
2095:
2050:
2019:
1962:
1925:
1888:
1847:
1763:
1730:
1689:
1640:
1617:
1566:
1507:
1474:
1433:
1384:
1361:
1310:
1275:
1235:
1177:
1142:
1119:
1078:
1027:
981:
924:
700:
660:
600:
577:
544:Minimum time for Cmax
527:
487:
441:
418:
416:{\displaystyle \tau }
381:
352:
33:
7058:Pharmacies of Norway
6995:Pharmacy informatics
6889:Pharmacoepidemiology
6798:Prehistoric medicine
6580:Reverse pharmacology
6490:Pharmacoepidemiology
6331:Biological half-life
6211:Ligand binding assay
6085:Activity at receptor
5979:Irreversible agonist
5654:, Java applications.
5505:improve this article
5078:Analytical Chemistry
5043:Analytical Chemistry
4936:. February 24, 2010.
4492:Cooperstown cocktail
4482:Biological half-life
3937:
3902:
3875:
3852:
3796:
3741:
3687:bioavailability and
3637:
3514:
3397:
3334:enzymatic inhibition
3263:This represents the
3151:
3130:within the organism
3004:
2978:
2951:
2891:
2881:first order kinetics
2805:or curve stripping.
2803:nonlinear regression
2645:
2555:
2534:
2504:
2407:
2383:
2308:
2268:
2244:
2183:
2152:
2110:
2102:1,320 h×mmol/L
2060:
2029:
1989:
1975:Area under the curve
1935:
1898:
1870:
1773:
1740:
1712:
1650:
1627:
1589:
1517:
1484:
1456:
1394:
1371:
1333:
1323:Absorption half-life
1285:
1245:
1204:
1152:
1129:
1101:
1037:
991:
953:
710:
670:
632:
587:
559:
497:
469:
428:
407:
362:
341:
269:biological membranes
244:in what is known as
71:pharmaceutical drugs
7005:Veterinary pharmacy
6937:Pharmacy technician
6899:Pharmacocybernetics
6793:History of pharmacy
6628:Combination therapy
6516:Pharmacoinformatics
6485:Medicinal chemistry
6091:Mechanism of action
5864:Educational centres
5811:Navigator Workbench
5517:footnote references
5375:2011EnST...45.2529J
5291:10.1208/aapsj070237
5165:20.500.11850/102558
5090:10.1021/ac50001a036
5055:10.1021/ac00125a022
4967:2010NatCo...1..100W
4368:organ transplants.
4269:Coagulation factors
4102:
4002:in many countries.
3894:Finally, using the
3713:Pharmaceutical form
3081:central compartment
2993:{\displaystyle t=0}
2772:veterinary medicine
2729:dynamic equilibrium
2206:
2077:
1085:55.0 h×mmol/L
607:Direct measurement
534:Direct measurement
304:
293:Amount of substance
208:(e.g. by metabolic
7000:Specialty pharmacy
6963:Community pharmacy
6932:Pharmacy residency
6598:Immunopharmacology
6548:Pharmacotoxicology
6449:Psychopharmacology
6241:Intrinsic activity
6141:Pleiotropy (drugs)
6062:Agonist-antagonist
5974:Endogenous agonist
5201:10.1007/BF01061728
4976:10.1038/ncomms1093
4406:. You can help by
4382:High risk to life.
4100:
3981:
3915:
3881:
3864:{\displaystyle Va}
3861:
3835:
3772:
3662:
3616:
3497:
3377:
3307:
3250:
3123:
3052:
2990:
2964:
2933:
2865:
2704:
2630:
2543:{\displaystyle \%}
2540:
2519:
2476:
2389:
2355:
2293:
2256:{\displaystyle CL}
2253:
2219:
2186:
2168:
2137:
2090:
2063:
2045:
2014:
1957:
1920:
1883:
1842:
1758:
1725:
1684:
1635:
1612:
1561:
1502:
1469:
1428:
1379:
1356:
1305:
1270:
1230:
1172:
1137:
1114:
1073:
1022:
976:
919:
695:
655:
595:
572:
522:
482:
436:
413:
376:
347:
302:
61:, is a branch of
37:
7096:
7095:
7053:Pharmacy in China
6980:Hospital pharmacy
6958:Clinical pharmacy
6894:Pharmacovigilance
6810:Prescription drug
6740:
6739:
6736:
6735:
6696:
6695:
6593:Photopharmacology
6588:
6587:
6561:
6560:
6534:
6533:
6498:
6497:
6461:
6460:
6454:Electrophysiology
6444:Neuropharmacology
6399:
6398:
6349:
6348:
6285:
6284:
6272:Therapeutic index
6224:
6223:
6169:
6168:
6118:
6117:
6047:
6046:
6002:
6001:
5783:MATLAB/SimBiology
5742:Phoenix/WinNonlin
5739:Entelos PhysioLab
5723:MATLAB/SimBiology
5675:Phoenix/WinNonlin
5671:MATLAB/SimBiology
5621:Compartment based
5606:Phoenix/WinNonlin
5598:MATLAB/SimBiology
5545:
5544:
5537:
5456:"Chemical safety"
5383:10.1021/es103092a
5150:(27): 7815–7818.
4902:Angewandte Chemie
4669:10.1002/jps.21009
4547:Plateau principle
4424:
4423:
4349:
4348:
4264:(HIV) medication
4120:Immunosuppressor
4036:mass spectrometry
4030:Mass spectrometry
4020:biological matrix
3979:
3833:
3614:
3605:
3566:
3495:
3338:positive feedback
3269:computer programs
3041:
3020:
2961:
2927:
2912:
2871:presupposes that
2845:chemical kinetics
2721:
2720:
2702:
2694:
2664:
2656:
2628:
2624:
2616:
2603:
2595:
2580:
2572:
2474:
2470:
2457:
2439:
2426:
2392:{\displaystyle f}
2353:
2331:
2318:
2133:
1945:
1880:
1840:
1837:
1815:
1808:
1722:
1682:
1679:
1605:
1559:
1552:
1466:
1426:
1423:
1349:
1317:83.3 mmol/L
1303:
1300:
1227:
1170:
1111:
1071:
1063:
972:
964:
931:27.7 mmol/L
914:
853:
789:
651:
643:
569:
537:60.9 mmol/L
479:
448:Design parameter
388:Design parameter
350:{\displaystyle D}
55:chemical kinetics
16:(Redirected from
7179:
7162:Pharmacokinetics
7147:
7146:
7136:
7104:
7086:
7085:
7048:Medication costs
7023:Drug development
6985:Nuclear pharmacy
6862:Pharmacogenomics
6850:Pharmacodynamics
6846:Pharmacokinetics
6767:
6760:
6753:
6744:
6698:
6658:
6638:Polypharmacology
6563:
6536:
6526:Pharmacogenomics
6521:Pharmacogenetics
6500:
6463:
6424:
6351:
6321:Rate of infusion
6296:
6291:Pharmacokinetics
6226:
6171:
6120:
6082:
6077:Pharmacodynamics
6057:Neurotransmitter
6039:Enzyme inhibitor
6004:
5959:
5939:
5932:
5925:
5916:
5853:Berkeley Madonna
5677:, PK Solutions,
5553:Noncompartmental
5540:
5533:
5529:
5526:
5520:
5488:
5487:
5480:
5470:
5469:
5467:
5466:
5452:
5446:
5445:
5443:
5442:
5427:
5421:
5420:
5418:
5417:
5401:
5395:
5394:
5358:
5352:
5338:
5332:
5331:
5319:
5313:
5312:
5302:
5279:The AAPS Journal
5270:
5264:
5263:
5227:
5221:
5220:
5184:
5178:
5177:
5167:
5138:
5132:
5131:
5129:
5127:
5117:
5108:
5102:
5101:
5073:
5067:
5066:
5038:
5032:
5031:
4995:
4989:
4988:
4978:
4946:
4940:
4937:
4925:
4897:
4891:
4876:
4867:
4866:
4844:
4838:
4837:
4821:
4815:
4800:
4791:
4790:
4783:
4777:
4776:
4775:
4774:
4751:
4745:
4744:
4743:
4742:
4719:
4713:
4712:
4710:
4709:
4703:
4696:
4687:
4681:
4680:
4652:
4646:
4645:
4627:
4621:
4620:
4610:
4601:(5): 1033–1082.
4586:
4580:
4568:
4512:Drug interaction
4502:Pharmacodynamics
4472:Bateman equation
4419:
4416:
4398:
4391:
4361:immunosuppressor
4103:
3990:
3988:
3987:
3982:
3980:
3972:
3961:
3947:
3924:
3922:
3921:
3916:
3890:
3888:
3887:
3882:
3870:
3868:
3867:
3862:
3844:
3842:
3841:
3836:
3834:
3829:
3809:
3781:
3779:
3778:
3773:
3671:
3669:
3668:
3663:
3625:
3623:
3622:
3617:
3615:
3613:
3612:
3611:
3606:
3603:
3597:
3596:
3574:
3573:
3572:
3567:
3564:
3558:
3557:
3535:
3530:
3529:
3524:
3523:
3506:
3504:
3503:
3498:
3496:
3494:
3493:
3492:
3480:
3479:
3454:
3453:
3452:
3437:
3436:
3414:
3409:
3408:
3259:
3257:
3256:
3251:
3248:
3247:
3223:
3222:
3204:
3203:
3185:
3184:
3166:
3165:
3061:
3059:
3058:
3053:
3051:
3050:
3043:
3042:
3039:
3022:
3021:
3018:
2999:
2997:
2996:
2991:
2973:
2971:
2970:
2965:
2963:
2962:
2959:
2942:
2940:
2939:
2934:
2929:
2928:
2925:
2913:
2911:
2903:
2895:
2816:trapezoidal rule
2713:
2711:
2710:
2705:
2703:
2698:
2697:
2696:
2695:
2692:
2672:
2667:
2666:
2665:
2662:
2657:
2654:
2639:
2637:
2636:
2631:
2629:
2627:
2626:
2625:
2622:
2617:
2614:
2607:
2606:
2605:
2604:
2601:
2596:
2593:
2583:
2582:
2581:
2578:
2573:
2570:
2562:
2549:
2547:
2546:
2541:
2528:
2526:
2525:
2520:
2485:
2483:
2482:
2477:
2475:
2473:
2472:
2471:
2468:
2459:
2458:
2455:
2442:
2441:
2440:
2437:
2428:
2427:
2424:
2411:
2398:
2396:
2395:
2390:
2364:
2362:
2361:
2356:
2354:
2352:
2338:
2333:
2332:
2329:
2320:
2319:
2316:
2302:
2300:
2299:
2294:
2292:
2287:
2282:
2281:
2276:
2262:
2260:
2259:
2254:
2228:
2226:
2225:
2220:
2215:
2205:
2194:
2177:
2175:
2174:
2169:
2167:
2159:
2146:
2144:
2143:
2138:
2136:
2135:
2134:
2131:
2099:
2097:
2096:
2091:
2086:
2076:
2071:
2054:
2052:
2051:
2046:
2044:
2036:
2023:
2021:
2020:
2015:
2013:
2012:
1966:
1964:
1963:
1958:
1947:
1946:
1943:
1929:
1927:
1926:
1921:
1919:
1915:
1892:
1890:
1889:
1884:
1882:
1881:
1878:
1851:
1849:
1848:
1843:
1841:
1839:
1838:
1835:
1829:
1821:
1816:
1814:
1813:
1809:
1801:
1794:
1777:
1767:
1765:
1764:
1759:
1757:
1756:
1748:
1734:
1732:
1731:
1726:
1724:
1723:
1720:
1693:
1691:
1690:
1685:
1683:
1681:
1680:
1677:
1671:
1654:
1644:
1642:
1641:
1636:
1634:
1621:
1619:
1618:
1613:
1611:
1610:
1606:
1598:
1570:
1568:
1567:
1562:
1560:
1558:
1557:
1553:
1545:
1538:
1521:
1511:
1509:
1508:
1503:
1501:
1500:
1492:
1478:
1476:
1475:
1470:
1468:
1467:
1464:
1437:
1435:
1434:
1429:
1427:
1425:
1424:
1421:
1415:
1398:
1388:
1386:
1385:
1380:
1378:
1365:
1363:
1362:
1357:
1355:
1354:
1350:
1342:
1314:
1312:
1311:
1306:
1304:
1302:
1301:
1298:
1289:
1279:
1277:
1276:
1271:
1269:
1265:
1239:
1237:
1236:
1231:
1229:
1228:
1225:
1216:
1215:
1181:
1179:
1178:
1173:
1171:
1169:
1168:
1156:
1146:
1144:
1143:
1138:
1136:
1123:
1121:
1120:
1115:
1113:
1112:
1109:
1082:
1080:
1079:
1074:
1072:
1067:
1066:
1065:
1064:
1061:
1041:
1031:
1029:
1028:
1023:
1021:
1017:
985:
983:
982:
977:
975:
974:
973:
970:
965:
962:
940:
928:
926:
925:
920:
915:
913:
912:
911:
907:
906:
882:
881:
877:
876:
859:
854:
852:
851:
850:
846:
845:
821:
820:
816:
815:
798:
790:
788:
778:
777:
765:
764:
754:
753:
752:
733:
728:
727:
704:
702:
701:
696:
694:
690:
664:
662:
661:
656:
654:
653:
652:
649:
644:
641:
619:
604:
602:
601:
596:
594:
581:
579:
578:
573:
571:
570:
567:
545:
531:
529:
528:
523:
521:
517:
491:
489:
488:
483:
481:
480:
477:
459:
445:
443:
442:
437:
435:
422:
420:
419:
414:
385:
383:
382:
377:
375:
356:
354:
353:
348:
305:
273:enzyme reactions
121:Pharmacokinetics
95:pharmacodynamics
40:Pharmacokinetics
21:
7187:
7186:
7182:
7181:
7180:
7178:
7177:
7176:
7152:
7151:
7150:
7106:
7105:
7101:
7097:
7092:
7074:
7009:
6946:
6942:Pharmacy school
6903:
6855:Pharmacometrics
6829:
6776:
6771:
6741:
6732:
6692:
6678:Drug resistance
6656:
6612:
6584:
6557:
6553:Neurotoxicology
6530:
6494:
6457:
6419:
6413:
6395:
6345:
6341:Bioavailability
6326:Onset of action
6281:
6220:
6165:
6114:
6071:
6043:
6034:Inverse agonist
5998:
5984:Partial agonist
5948:
5943:
5866:
5550:
5541:
5530:
5524:
5521:
5502:
5493:This article's
5489:
5485:
5478:
5473:
5464:
5462:
5454:
5453:
5449:
5440:
5438:
5429:
5428:
5424:
5415:
5413:
5403:
5402:
5398:
5360:
5359:
5355:
5339:
5335:
5321:
5320:
5316:
5272:
5271:
5267:
5229:
5228:
5224:
5186:
5185:
5181:
5140:
5139:
5135:
5125:
5123:
5115:
5110:
5109:
5105:
5075:
5074:
5070:
5049:(12): 2453–60.
5040:
5039:
5035:
4997:
4996:
4992:
4948:
4947:
4943:
4928:
4908:(12): 2238–41.
4899:
4898:
4894:
4877:
4870:
4863:
4846:
4845:
4841:
4823:
4822:
4818:
4814:, 9788429155358
4804:Farmacocinética
4801:
4794:
4785:
4784:
4780:
4772:
4770:
4753:
4752:
4748:
4740:
4738:
4721:
4720:
4716:
4707:
4705:
4701:
4694:
4689:
4688:
4684:
4654:
4653:
4649:
4642:
4629:
4628:
4624:
4588:
4587:
4583:
4569:
4565:
4561:
4556:
4522:Pharmacometrics
4497:Enzyme kinetics
4487:Bioavailability
4467:
4420:
4414:
4411:
4404:needs expansion
4389:
4098:
4081:
4032:
4013:
4008:
3935:
3934:
3900:
3899:
3873:
3872:
3850:
3849:
3810:
3794:
3793:
3739:
3738:
3635:
3634:
3601:
3588:
3575:
3562:
3549:
3536:
3517:
3512:
3511:
3484:
3468:
3455:
3441:
3428:
3415:
3400:
3395:
3394:
3383:
3381:Bioavailability
3369:
3367:Bioavailability
3236:
3211:
3192:
3173:
3157:
3149:
3148:
3142:
3135:
3115:
3109:
3068:
3034:
3026:
3013:
3002:
3001:
2976:
2975:
2954:
2949:
2948:
2920:
2904:
2896:
2889:
2888:
2857:
2833:
2811:
2795:bioavailability
2746:
2739:
2735:
2680:
2673:
2648:
2643:
2642:
2608:
2587:
2564:
2563:
2553:
2552:
2532:
2531:
2502:
2501:
2463:
2450:
2443:
2432:
2419:
2412:
2405:
2404:
2381:
2380:
2373:Bioavailability
2342:
2324:
2311:
2306:
2305:
2271:
2266:
2265:
2242:
2241:
2181:
2180:
2150:
2149:
2119:
2108:
2107:
2058:
2057:
2027:
2026:
1998:
1987:
1986:
1969:50 mmol/h
1938:
1933:
1932:
1896:
1895:
1873:
1868:
1867:
1830:
1822:
1795:
1778:
1771:
1770:
1743:
1738:
1737:
1715:
1710:
1709:
1672:
1655:
1648:
1647:
1625:
1624:
1592:
1587:
1586:
1539:
1522:
1515:
1514:
1487:
1482:
1481:
1459:
1454:
1453:
1416:
1399:
1392:
1391:
1369:
1368:
1336:
1331:
1330:
1293:
1283:
1282:
1243:
1242:
1220:
1207:
1202:
1201:
1160:
1150:
1149:
1127:
1126:
1104:
1099:
1098:
1049:
1042:
1035:
1034:
989:
988:
956:
951:
950:
936:
898:
890:
883:
868:
860:
837:
829:
822:
807:
799:
769:
756:
755:
744:
734:
713:
708:
707:
668:
667:
635:
630:
629:
615:
585:
584:
562:
557:
556:
552:
543:
495:
494:
472:
467:
466:
457:
426:
425:
405:
404:
397:Dosing interval
360:
359:
339:
338:
324:
308:Characteristic
281:
214:cytochrome P450
149:
143:
138:
117:
103:adverse effects
101:, benefit, and
28:
23:
22:
15:
12:
11:
5:
7185:
7183:
7175:
7174:
7169:
7164:
7154:
7153:
7149:
7148:
7098:
7094:
7093:
7091:
7090:
7079:
7076:
7075:
7073:
7072:
7071:
7070:
7060:
7055:
7050:
7045:
7040:
7035:
7030:
7028:Drug discovery
7025:
7019:
7017:
7011:
7010:
7008:
7007:
7002:
6997:
6992:
6987:
6982:
6977:
6972:
6971:
6970:
6960:
6954:
6952:
6951:Practice areas
6948:
6947:
6945:
6944:
6939:
6934:
6929:
6927:Pharmaconomist
6924:
6923:
6922:
6911:
6909:
6905:
6904:
6902:
6901:
6896:
6891:
6886:
6881:
6876:
6871:
6870:
6869:
6864:
6859:
6858:
6857:
6837:
6835:
6831:
6830:
6828:
6827:
6822:
6817:
6812:
6807:
6802:
6801:
6800:
6790:
6784:
6782:
6778:
6777:
6772:
6770:
6769:
6762:
6755:
6747:
6738:
6737:
6734:
6733:
6731:
6730:
6725:
6720:
6718:Bacteriostatic
6715:
6710:
6704:
6702:
6694:
6693:
6691:
6690:
6685:
6680:
6675:
6670:
6668:Drug tolerance
6664:
6662:
6655:
6650:
6648:Lists of drugs
6645:
6640:
6635:
6630:
6625:
6620:
6618:
6614:
6613:
6611:
6610:
6605:
6600:
6595:
6589:
6586:
6585:
6583:
6582:
6577:
6571:
6569:
6567:Drug discovery
6559:
6558:
6556:
6555:
6550:
6544:
6542:
6532:
6531:
6529:
6528:
6523:
6518:
6512:
6510:
6496:
6495:
6493:
6492:
6487:
6482:
6477:
6471:
6469:
6459:
6458:
6456:
6451:
6446:
6441:
6436:
6434:
6421:
6415:
6414:
6412:
6411:
6409:Bioequivalence
6406:
6400:
6397:
6396:
6394:
6393:
6383:
6378:
6373:
6368:
6357:
6355:
6347:
6346:
6344:
6343:
6338:
6333:
6328:
6323:
6318:
6308:
6302:
6300:
6293:
6287:
6286:
6283:
6282:
6280:
6279:
6274:
6269:
6243:
6238:
6232:
6230:
6222:
6221:
6219:
6218:
6203:
6198:
6193:
6188:
6183:
6177:
6175:
6167:
6166:
6164:
6163:
6153:
6151:Adverse effect
6148:
6143:
6138:
6126:
6124:
6116:
6115:
6113:
6108:
6103:
6098:
6096:Mode of action
6093:
6088:
6086:
6079:
6073:
6072:
6070:
6069:
6064:
6059:
6054:
6048:
6045:
6044:
6042:
6041:
6036:
6031:
6026:
6021:
6016:
6010:
6008:
6000:
5999:
5997:
5996:
5991:
5986:
5981:
5976:
5971:
5965:
5963:
5956:
5950:
5949:
5944:
5942:
5941:
5934:
5927:
5919:
5865:
5862:
5861:
5860:
5837:
5836:
5832:
5831:
5820:
5819:
5815:
5814:
5771:
5755:
5754:
5750:
5749:
5746:ADME Workbench
5703:
5696:
5695:
5691:
5690:
5655:
5623:
5622:
5618:
5617:
5578:
5555:
5554:
5549:
5546:
5543:
5542:
5497:external links
5492:
5490:
5483:
5477:
5476:External links
5474:
5472:
5471:
5447:
5422:
5396:
5369:(7): 2529–40.
5353:
5333:
5314:
5285:(2): E363–73.
5265:
5238:(3): 294–305.
5222:
5179:
5133:
5103:
5068:
5033:
4990:
4941:
4939:
4938:
4892:
4868:
4861:
4839:
4816:
4792:
4778:
4746:
4714:
4682:
4647:
4640:
4622:
4581:
4562:
4560:
4557:
4555:
4554:
4552:Toxicokinetics
4549:
4544:
4539:
4534:
4532:Bioequivalence
4529:
4524:
4519:
4514:
4509:
4504:
4499:
4494:
4489:
4484:
4479:
4474:
4468:
4466:
4463:
4422:
4421:
4401:
4399:
4388:
4385:
4384:
4383:
4380:
4377:
4365:nephrotoxicity
4347:
4346:
4345:
4344:
4339:
4333:
4327:
4319:
4318:
4317:
4312:
4301:
4300:
4299:
4294:
4292:5-Fluorouracil
4289:
4282:
4281:
4280:
4272:
4271:
4266:
4258:
4250:
4245:Bronchodilator
4241:
4240:
4239:
4238:
4233:
4228:
4223:
4216:
4215:
4214:
4209:
4204:
4199:
4194:
4187:
4186:
4185:
4180:
4173:
4172:
4171:
4166:
4161:
4156:
4151:
4146:
4141:
4133:
4132:
4124:
4118:
4112:
4097:
4094:
4089:kidney failure
4080:
4077:
4031:
4028:
4012:
4009:
4007:
4004:
3996:bioequivalence
3992:
3991:
3978:
3975:
3970:
3967:
3964:
3960:
3957:
3954:
3950:
3946:
3943:
3913:
3910:
3907:
3880:
3860:
3857:
3846:
3845:
3832:
3828:
3825:
3822:
3819:
3816:
3813:
3807:
3804:
3801:
3783:
3782:
3770:
3767:
3764:
3761:
3758:
3755:
3752:
3749:
3746:
3732:
3731:
3726:
3723:
3718:
3715:
3703:
3702:
3681:effective dose
3673:
3672:
3660:
3657:
3654:
3651:
3648:
3645:
3642:
3627:
3626:
3610:
3600:
3595:
3591:
3587:
3584:
3581:
3578:
3571:
3561:
3556:
3552:
3548:
3545:
3542:
3539:
3533:
3528:
3522:
3508:
3507:
3491:
3487:
3483:
3478:
3475:
3471:
3467:
3464:
3461:
3458:
3451:
3448:
3444:
3440:
3435:
3431:
3427:
3424:
3421:
3418:
3412:
3407:
3403:
3379:Main article:
3368:
3365:
3361:
3360:
3357:
3330:
3323:
3320:
3319:
3318:
3315:
3312:
3261:
3260:
3246:
3243:
3239:
3235:
3232:
3229:
3226:
3221:
3218:
3214:
3210:
3207:
3202:
3199:
3195:
3191:
3188:
3183:
3180:
3176:
3172:
3169:
3164:
3160:
3156:
3140:
3133:
3108:
3105:
3067:
3064:
3049:
3046:
3037:
3033:
3029:
3025:
3016:
3012:
3009:
2989:
2986:
2983:
2957:
2932:
2923:
2919:
2916:
2910:
2907:
2902:
2899:
2856:
2853:
2849:thermodynamics
2832:
2829:
2810:
2807:
2767:bioequivalence
2761:and above all
2745:
2742:
2737:
2733:
2719:
2718:
2715:
2701:
2690:
2687:
2683:
2679:
2676:
2670:
2660:
2651:
2620:
2611:
2599:
2590:
2586:
2576:
2567:
2560:
2550:
2539:
2529:
2518:
2515:
2512:
2509:
2499:
2496:
2490:
2489:
2486:
2466:
2462:
2453:
2449:
2446:
2435:
2431:
2422:
2418:
2415:
2402:
2399:
2388:
2378:
2375:
2369:
2368:
2367:0.38 L/h
2365:
2351:
2348:
2345:
2341:
2336:
2327:
2323:
2314:
2303:
2291:
2286:
2280:
2275:
2263:
2252:
2249:
2239:
2236:
2230:
2229:
2218:
2214:
2209:
2204:
2201:
2198:
2193:
2189:
2178:
2166:
2162:
2158:
2147:
2129:
2126:
2122:
2118:
2115:
2104:
2103:
2100:
2089:
2085:
2080:
2075:
2070:
2066:
2055:
2043:
2039:
2035:
2024:
2011:
2008:
2005:
2001:
1997:
1994:
1984:
1977:
1971:
1970:
1967:
1956:
1953:
1950:
1941:
1930:
1918:
1914:
1910:
1907:
1904:
1893:
1876:
1865:
1862:
1856:
1855:
1854:0.0578 h
1852:
1833:
1828:
1825:
1819:
1812:
1807:
1804:
1798:
1793:
1790:
1787:
1784:
1781:
1768:
1755:
1752:
1747:
1735:
1718:
1707:
1704:
1698:
1697:
1694:
1675:
1670:
1667:
1664:
1661:
1658:
1645:
1633:
1622:
1609:
1604:
1601:
1595:
1584:
1581:
1575:
1574:
1571:
1556:
1551:
1548:
1542:
1537:
1534:
1531:
1528:
1525:
1512:
1499:
1496:
1491:
1479:
1462:
1451:
1448:
1442:
1441:
1438:
1419:
1414:
1411:
1408:
1405:
1402:
1389:
1377:
1366:
1353:
1348:
1345:
1339:
1328:
1325:
1319:
1318:
1315:
1296:
1292:
1280:
1268:
1264:
1260:
1257:
1254:
1251:
1240:
1223:
1219:
1214:
1210:
1199:
1192:
1186:
1185:
1182:
1167:
1163:
1159:
1147:
1135:
1124:
1107:
1096:
1093:
1087:
1086:
1083:
1070:
1059:
1056:
1052:
1048:
1045:
1032:
1020:
1016:
1012:
1009:
1006:
1003:
1000:
997:
986:
968:
959:
948:
941:
933:
932:
929:
918:
910:
905:
901:
897:
893:
889:
886:
880:
875:
871:
867:
863:
857:
849:
844:
840:
836:
832:
828:
825:
819:
814:
810:
806:
802:
796:
793:
787:
784:
781:
776:
772:
768:
763:
759:
751:
747:
743:
740:
737:
731:
726:
723:
720:
716:
705:
693:
689:
685:
682:
679:
676:
665:
647:
638:
627:
620:
612:
611:
608:
605:
593:
582:
565:
554:
550:
547:
539:
538:
535:
532:
520:
516:
512:
509:
506:
503:
492:
475:
464:
461:
453:
452:
449:
446:
434:
423:
412:
402:
399:
393:
392:
391:500 mmol
389:
386:
374:
371:
368:
357:
346:
336:
333:
327:
326:
323:Worked example
321:
318:
315:
312:
309:
280:
277:
241:
240:
221:
194:
183:
172:
145:Main article:
142:
139:
136:
135:
132:
112:
111:
79:food additives
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
7184:
7173:
7170:
7168:
7165:
7163:
7160:
7159:
7157:
7144:
7140:
7135:
7130:
7126:
7122:
7118:
7114:
7110:
7103:
7100:
7089:
7081:
7080:
7077:
7069:
7066:
7065:
7064:
7061:
7059:
7056:
7054:
7051:
7049:
7046:
7044:
7041:
7039:
7036:
7034:
7031:
7029:
7026:
7024:
7021:
7020:
7018:
7016:
7012:
7006:
7003:
7001:
6998:
6996:
6993:
6991:
6988:
6986:
6983:
6981:
6978:
6976:
6973:
6969:
6966:
6965:
6964:
6961:
6959:
6956:
6955:
6953:
6949:
6943:
6940:
6938:
6935:
6933:
6930:
6928:
6925:
6921:
6918:
6917:
6916:
6913:
6912:
6910:
6906:
6900:
6897:
6895:
6892:
6890:
6887:
6885:
6884:Pharmacognosy
6882:
6880:
6879:Pharmaceutics
6877:
6875:
6872:
6868:
6865:
6863:
6860:
6856:
6853:
6852:
6851:
6847:
6844:
6843:
6842:
6839:
6838:
6836:
6832:
6826:
6823:
6821:
6818:
6816:
6813:
6811:
6808:
6806:
6803:
6799:
6796:
6795:
6794:
6791:
6789:
6786:
6785:
6783:
6779:
6775:
6768:
6763:
6761:
6756:
6754:
6749:
6748:
6745:
6729:
6726:
6724:
6721:
6719:
6716:
6714:
6711:
6709:
6706:
6705:
6703:
6699:
6689:
6686:
6684:
6681:
6679:
6676:
6674:
6673:Tachyphylaxis
6671:
6669:
6666:
6665:
6663:
6659:
6654:
6651:
6649:
6646:
6644:
6641:
6639:
6636:
6634:
6631:
6629:
6626:
6624:
6621:
6619:
6615:
6609:
6606:
6604:
6601:
6599:
6596:
6594:
6591:
6590:
6581:
6578:
6576:
6573:
6572:
6570:
6568:
6564:
6554:
6551:
6549:
6546:
6545:
6543:
6541:
6537:
6527:
6524:
6522:
6519:
6517:
6514:
6513:
6511:
6509:
6505:
6501:
6491:
6488:
6486:
6483:
6481:
6478:
6476:
6473:
6472:
6470:
6468:
6464:
6455:
6452:
6450:
6447:
6445:
6442:
6440:
6437:
6435:
6433:
6429:
6425:
6422:
6416:
6410:
6407:
6405:
6402:
6401:
6391:
6387:
6384:
6382:
6379:
6377:
6374:
6372:
6369:
6366:
6362:
6359:
6358:
6356:
6352:
6342:
6339:
6337:
6334:
6332:
6329:
6327:
6324:
6322:
6319:
6316:
6312:
6309:
6307:
6304:
6303:
6301:
6297:
6294:
6292:
6288:
6278:
6275:
6273:
6270:
6267:
6263:
6259:
6255:
6251:
6247:
6244:
6242:
6239:
6237:
6234:
6233:
6231:
6227:
6216:
6212:
6208:
6204:
6202:
6199:
6197:
6194:
6192:
6189:
6187:
6184:
6182:
6179:
6178:
6176:
6172:
6161:
6160:Neurotoxicity
6157:
6154:
6152:
6149:
6147:
6144:
6142:
6139:
6136:
6132:
6129:Selectivity (
6128:
6127:
6125:
6121:
6112:
6109:
6107:
6104:
6102:
6099:
6097:
6094:
6092:
6089:
6087:
6083:
6080:
6078:
6074:
6068:
6067:Pharmacophore
6065:
6063:
6060:
6058:
6055:
6053:
6050:
6049:
6040:
6037:
6035:
6032:
6030:
6027:
6025:
6022:
6020:
6017:
6015:
6012:
6011:
6009:
6005:
5995:
5992:
5990:
5987:
5985:
5982:
5980:
5977:
5975:
5972:
5970:
5967:
5966:
5964:
5960:
5957:
5955:
5951:
5947:
5940:
5935:
5933:
5928:
5926:
5921:
5920:
5917:
5913:
5911:
5907:
5903:
5899:
5895:
5891:
5890:San Francisco
5887:
5883:
5879:
5875:
5871:
5863:
5858:
5854:
5850:
5846:
5842:
5841:
5840:
5834:
5833:
5830:
5826:
5822:
5821:
5817:
5816:
5812:
5808:
5804:
5801:for SAAM II,
5800:
5796:
5792:
5788:
5784:
5780:
5776:
5772:
5769:
5765:
5761:
5757:
5756:
5753:Population PK
5752:
5751:
5747:
5743:
5740:
5736:
5732:
5728:
5724:
5720:
5716:
5712:
5708:
5704:
5702:
5698:
5697:
5693:
5692:
5688:
5684:
5680:
5676:
5672:
5668:
5664:
5660:
5656:
5653:
5649:
5645:
5641:
5637:
5633:
5629:
5625:
5624:
5620:
5619:
5615:
5611:
5607:
5603:
5599:
5595:
5591:
5587:
5583:
5579:
5577:
5573:
5569:
5565:
5561:
5557:
5556:
5552:
5551:
5547:
5539:
5536:
5528:
5518:
5514:
5513:inappropriate
5510:
5506:
5500:
5498:
5491:
5482:
5481:
5475:
5461:
5457:
5451:
5448:
5437:
5433:
5426:
5423:
5412:on 2012-04-05
5411:
5407:
5400:
5397:
5392:
5388:
5384:
5380:
5376:
5372:
5368:
5364:
5357:
5354:
5351:
5350:84-8174-658-4
5347:
5343:
5337:
5334:
5329:
5325:
5318:
5315:
5310:
5306:
5301:
5296:
5292:
5288:
5284:
5280:
5276:
5269:
5266:
5261:
5257:
5253:
5249:
5245:
5241:
5237:
5233:
5226:
5223:
5218:
5214:
5210:
5206:
5202:
5198:
5195:(5): 445–79.
5194:
5190:
5183:
5180:
5175:
5171:
5166:
5161:
5157:
5153:
5149:
5145:
5137:
5134:
5121:
5114:
5107:
5104:
5099:
5095:
5091:
5087:
5084:(2): 474–81.
5083:
5079:
5072:
5069:
5064:
5060:
5056:
5052:
5048:
5044:
5037:
5034:
5029:
5025:
5021:
5017:
5013:
5009:
5006:(5): 479–89.
5005:
5001:
4994:
4991:
4986:
4982:
4977:
4972:
4968:
4964:
4960:
4956:
4952:
4945:
4942:
4935:
4931:
4927:
4926:
4923:
4919:
4915:
4911:
4907:
4903:
4896:
4893:
4889:
4888:84-7978-147-5
4885:
4881:
4875:
4873:
4869:
4864:
4862:91-86274-92-9
4858:
4854:
4850:
4843:
4840:
4835:
4831:
4827:
4820:
4817:
4813:
4812:84-291-5535-X
4809:
4805:
4799:
4797:
4793:
4788:
4782:
4779:
4769:
4765:
4761:
4757:
4750:
4747:
4737:
4733:
4729:
4725:
4718:
4715:
4704:on 2016-05-08
4700:
4693:
4686:
4683:
4678:
4674:
4670:
4666:
4663:(2): 654–90.
4662:
4658:
4651:
4648:
4643:
4641:3-609-64970-4
4637:
4633:
4626:
4623:
4618:
4614:
4609:
4604:
4600:
4596:
4592:
4585:
4582:
4579:
4575:
4574:
4567:
4564:
4558:
4553:
4550:
4548:
4545:
4543:
4540:
4538:
4537:Generic drugs
4535:
4533:
4530:
4528:
4525:
4523:
4520:
4518:
4515:
4513:
4510:
4508:
4505:
4503:
4500:
4498:
4495:
4493:
4490:
4488:
4485:
4483:
4480:
4478:
4475:
4473:
4470:
4469:
4464:
4462:
4460:
4456:
4452:
4448:
4444:
4443:safety trials
4440:
4436:
4432:
4431:microplastics
4428:
4427:Ecotoxicology
4418:
4409:
4405:
4402:This section
4400:
4397:
4393:
4392:
4387:Ecotoxicology
4386:
4381:
4379:High toxicity
4378:
4375:
4374:
4373:
4369:
4366:
4362:
4358:
4353:
4343:
4340:
4337:
4334:
4331:
4328:
4325:
4322:
4321:
4320:
4316:
4313:
4311:
4308:
4307:
4306:
4302:
4298:
4295:
4293:
4290:
4288:
4285:
4284:
4283:
4279:
4276:
4275:
4274:
4273:
4270:
4267:
4265:
4262:
4259:
4257:
4254:
4251:
4249:
4246:
4243:
4242:
4237:
4234:
4232:
4229:
4227:
4224:
4222:
4219:
4218:
4217:
4213:
4212:Mycophenolate
4210:
4208:
4205:
4203:
4200:
4198:
4195:
4193:
4190:
4189:
4188:
4184:
4181:
4179:
4176:
4175:
4174:
4170:
4167:
4165:
4164:Phenobarbital
4162:
4160:
4157:
4155:
4152:
4150:
4149:Valproic acid
4147:
4145:
4144:Carbamazepine
4142:
4140:
4137:
4136:
4135:
4134:
4131:
4128:
4125:
4123:
4119:
4117:
4114:Cardioactive
4113:
4111:
4108:
4107:Antiepileptic
4105:
4104:
4095:
4093:
4090:
4085:
4078:
4076:
4074:
4070:
4066:
4061:
4059:
4055:
4054:curve fitting
4050:
4046:
4042:
4037:
4029:
4027:
4025:
4021:
4017:
4010:
4005:
4003:
4001:
4000:generic drugs
3997:
3976:
3973:
3968:
3965:
3962:
3948:
3933:
3932:
3931:
3928:
3911:
3908:
3905:
3897:
3892:
3878:
3858:
3855:
3830:
3826:
3823:
3820:
3817:
3814:
3811:
3805:
3802:
3799:
3792:
3791:
3790:
3788:
3768:
3765:
3762:
3759:
3756:
3753:
3750:
3747:
3744:
3737:
3736:
3735:
3730:
3727:
3724:
3722:
3719:
3717:Chemical form
3716:
3714:
3711:
3710:
3709:
3706:
3700:
3697:
3696:
3695:
3692:
3690:
3686:
3682:
3678:
3658:
3655:
3652:
3649:
3646:
3643:
3640:
3633:
3632:
3631:
3608:
3598:
3593:
3585:
3582:
3579:
3569:
3559:
3554:
3546:
3543:
3540:
3531:
3526:
3510:
3509:
3489:
3485:
3481:
3476:
3473:
3465:
3462:
3459:
3449:
3446:
3442:
3438:
3433:
3425:
3422:
3419:
3410:
3405:
3401:
3393:
3392:
3391:
3388:
3382:
3373:
3366:
3364:
3358:
3355:
3351:
3347:
3343:
3339:
3335:
3332:Induction or
3331:
3328:
3324:
3321:
3316:
3313:
3309:
3308:
3303:
3297:
3296:intravenously
3293:
3292:
3291:
3289:
3285:
3281:
3276:
3274:
3270:
3266:
3244:
3241:
3237:
3233:
3230:
3227:
3224:
3219:
3216:
3212:
3208:
3205:
3200:
3197:
3193:
3189:
3186:
3181:
3178:
3174:
3170:
3167:
3162:
3158:
3154:
3147:
3146:
3145:
3143:
3136:
3129:
3119:
3114:
3106:
3104:
3101:
3097:
3092:
3090:
3086:
3082:
3077:
3073:
3065:
3063:
3047:
3044:
3035:
3031:
3027:
3023:
3014:
3010:
3007:
2987:
2984:
2981:
2955:
2946:
2930:
2921:
2917:
2914:
2908:
2905:
2900:
2897:
2886:
2882:
2877:
2874:
2870:
2861:
2854:
2852:
2850:
2846:
2842:
2838:
2830:
2828:
2825:
2821:
2817:
2808:
2806:
2804:
2800:
2796:
2792:
2788:
2784:
2780:
2775:
2773:
2768:
2764:
2760:
2756:
2752:
2751:compartmental
2743:
2741:
2730:
2726:
2716:
2714:
2699:
2688:
2685:
2681:
2677:
2674:
2668:
2658:
2649:
2618:
2609:
2597:
2588:
2584:
2574:
2565:
2558:
2551:
2530:
2516:
2513:
2510:
2500:
2497:
2495:
2492:
2491:
2487:
2464:
2460:
2451:
2447:
2444:
2433:
2429:
2420:
2416:
2413:
2403:
2400:
2386:
2379:
2376:
2374:
2371:
2370:
2366:
2349:
2346:
2343:
2339:
2334:
2325:
2321:
2312:
2304:
2284:
2278:
2264:
2250:
2247:
2240:
2237:
2235:
2232:
2231:
2216:
2207:
2202:
2199:
2196:
2191:
2187:
2179:
2160:
2148:
2127:
2124:
2120:
2116:
2113:
2106:
2105:
2087:
2078:
2068:
2064:
2056:
2037:
2025:
2006:
2003:
1999:
1995:
1992:
1985:
1982:
1976:
1972:
1968:
1954:
1951:
1948:
1939:
1931:
1912:
1894:
1874:
1866:
1863:
1861:
1860:Infusion rate
1858:
1857:
1853:
1831:
1826:
1823:
1817:
1810:
1805:
1802:
1796:
1788:
1782:
1779:
1769:
1753:
1750:
1736:
1716:
1708:
1705:
1703:
1700:
1699:
1695:
1673:
1665:
1659:
1656:
1646:
1623:
1607:
1602:
1599:
1593:
1585:
1582:
1580:
1577:
1576:
1573:0.693 h
1572:
1554:
1549:
1546:
1540:
1532:
1526:
1523:
1513:
1497:
1494:
1480:
1460:
1452:
1449:
1447:
1444:
1443:
1439:
1417:
1409:
1403:
1400:
1390:
1367:
1351:
1346:
1343:
1337:
1329:
1326:
1324:
1321:
1320:
1316:
1294:
1290:
1281:
1262:
1241:
1221:
1217:
1212:
1208:
1200:
1197:
1193:
1191:
1190:Concentration
1188:
1187:
1183:
1165:
1161:
1157:
1148:
1125:
1105:
1097:
1094:
1092:
1089:
1088:
1084:
1068:
1057:
1054:
1050:
1046:
1043:
1033:
1014:
998:
987:
966:
957:
949:
946:
942:
939:
935:
934:
930:
908:
903:
899:
895:
891:
887:
884:
878:
873:
869:
865:
861:
855:
847:
842:
838:
834:
830:
826:
823:
817:
812:
808:
804:
800:
791:
782:
779:
774:
770:
761:
757:
749:
745:
741:
738:
735:
729:
724:
721:
718:
714:
706:
687:
666:
645:
636:
628:
625:
621:
618:
614:
613:
609:
606:
583:
563:
555:
548:
546:
541:
540:
536:
533:
514:
493:
473:
465:
462:
460:
455:
454:
450:
447:
424:
410:
403:
400:
398:
395:
394:
390:
387:
358:
344:
337:
334:
332:
329:
328:
322:
319:
316:
313:
310:
307:
306:
300:
298:
294:
290:
286:
278:
276:
274:
270:
266:
262:
257:
255:
251:
247:
238:
234:
230:
228:
227:
222:
219:
215:
211:
207:
203:
201:
200:
195:
192:
190:
189:
184:
181:
179:
178:
173:
170:
166:
162:
160:
159:
154:
153:
152:
148:
140:
133:
130:
126:
125:
124:
122:
115:
110:
108:
105:, as seen in
104:
100:
96:
92:
88:
84:
80:
76:
72:
68:
64:
60:
56:
52:
48:
45:
44:Ancient Greek
41:
32:
19:
7119:(6): 924–6.
7116:
7112:
7102:
6845:
6841:Pharmacology
6643:Chemotherapy
6603:Cell biology
6504:Biochemistry
6428:Neuroscience
6376:Distribution
6306:Loading dose
6290:
5989:Superagonist
5946:Pharmacology
5867:
5838:
5823:Commercial:
5795:Phoenix/NLME
5781:, Kinetica,
5773:Commercial:
5705:Commercial:
5679:PottersWheel
5669:, Kinetica,
5657:Commercial:
5610:PK Solutions
5580:Commercial:
5531:
5522:
5507:by removing
5494:
5463:. Retrieved
5459:
5450:
5439:. Retrieved
5435:
5425:
5414:. Retrieved
5410:the original
5399:
5366:
5362:
5356:
5336:
5327:
5317:
5282:
5278:
5268:
5235:
5231:
5225:
5192:
5188:
5182:
5147:
5143:
5136:
5124:. Retrieved
5106:
5081:
5077:
5071:
5046:
5042:
5036:
5003:
4999:
4993:
4958:
4954:
4944:
4933:
4905:
4901:
4895:
4879:
4852:
4842:
4833:
4829:
4819:
4803:
4781:
4771:, retrieved
4759:
4749:
4739:, retrieved
4727:
4717:
4706:. Retrieved
4699:the original
4685:
4660:
4656:
4650:
4631:
4625:
4598:
4594:
4584:
4571:
4566:
4425:
4412:
4408:adding to it
4403:
4370:
4354:
4350:
4287:Methotrexate
4278:Theophylline
4263:
4255:
4247:
4159:Ethosuximide
4129:
4121:
4115:
4109:
4083:
4082:
4062:
4033:
4014:
3993:
3893:
3847:
3786:
3784:
3733:
3707:
3704:
3698:
3693:
3688:
3684:
3676:
3674:
3628:
3384:
3362:
3283:
3277:
3264:
3262:
3138:
3131:
3124:
3093:
3084:
3080:
3072:blood supply
3069:
2884:
2878:
2873:blood plasma
2868:
2866:
2837:compartments
2836:
2834:
2823:
2812:
2776:
2762:
2758:
2747:
2725:steady state
2724:
2722:
2640:
945:steady state
622:The lowest (
311:Description
299:by scaling.
282:
260:
258:
249:
245:
242:
225:
224:
198:
197:
187:
186:
176:
175:
157:
156:
150:
120:
119:
107:PK/PD models
63:pharmacology
58:
50:
46:
39:
38:
6908:Professions
6788:Compounding
6728:Bactericide
6404:Compartment
6215:Patch clamp
6191:Schild plot
5799:PopKinetics
5460:www.who.int
5436:www.epa.gov
5404:Ashauer R.
4756:"Half Life"
4724:"Half Life"
4517:Patlak plot
4459:lethal dose
4357:ciclosporin
4336:Factor VIIa
4324:Factor VIII
4256:medication
4248:medication
4192:Ciclosporin
4154:Lamotrigine
4130:medication
4122:medication
4116:medication
4110:medication
4065:microdosing
3387:intravenous
3342:fluvoxamine
2494:Fluctuation
1440:1.0 h
1184:6.0 L
610:3.9 h
254:elimination
237:body tissue
206:metabolites
191:istribution
167:. See also
129:metabolites
49:"drug" and
7156:Categories
6915:Pharmacist
6867:Toxicology
6805:Medication
6608:Physiology
6540:Toxicology
6432:psychology
6381:Metabolism
6371:Absorption
6365:Liberation
6207:Organ bath
6135:Functional
6014:Antagonist
6007:Inhibitory
5962:Excitatory
5906:Manchester
5902:Washington
5878:Gothenburg
5843:Freeware:
5835:Simulation
5758:Freeware:
5719:GastroPlus
5699:Freeware:
5626:Freeware:
5558:Freeware:
5465:2022-05-15
5441:2022-05-15
5416:2011-12-03
5328:Nefrologia
4961:(7): 100.
4773:2023-05-23
4760:StatPearls
4741:2021-12-25
4728:StatPearls
4708:2011-04-04
4559:References
4439:pesticides
4433:and other
4415:April 2019
4297:Irinotecan
4253:Cytostatic
4236:Vancomycin
4226:Tobramycin
4221:Gentamicin
4207:Everolimus
4197:Tacrolimus
4127:Antibiotic
4058:quadratics
3729:Metabolism
3346:fluoxetine
3327:saturation
3325:Enzymatic
2799:solubility
1696:12 h
451:24 h
287:(mol) and
265:excipients
116:definition
87:metabolism
75:pesticides
67:xenobiotic
6390:Clearance
6386:Excretion
6205:Methods (
5910:Sheffield
5896:, Tokyo,
5829:PrecisePK
5807:DoseMe-Rx
5779:PrecisePK
5731:ProcessDB
5683:ProcessDB
5667:Imalytics
5663:PrecisePK
5590:EquivTest
5572:MetidaNCA
5509:excessive
4435:biosphere
4342:Factor XI
4330:Factor IX
4315:Ritonavir
4310:Tenofovir
4305:Efavirenz
4261:Antiviral
4202:Sirolimus
4183:Lidocaine
4169:Primidone
4139:Phenytoin
3969:
3879:τ
3831:τ
3824:⋅
3818:⋅
3766:⋅
3757:⋅
3725:Stability
3653:⋅
3599:⋅
3560:⋅
3482:⋅
3439:⋅
3350:phenytoin
3228:⋯
3045:×
3032:−
3024:×
2918:−
2753:methods.
2700:τ
2686:τ
2585:−
2538:%
2508:%
2461:⋅
2430:⋅
2322:⋅
2234:Clearance
2203:τ
2188:∫
2161:⋅
2125:τ
2074:∞
2065:∫
2038:⋅
2010:∞
2007:−
1949:⋅
1783:
1751:−
1660:
1527:
1495:−
1404:
1069:τ
1055:τ
999:×
909:τ
896:−
888:−
879:τ
866:−
856:−
848:τ
835:−
827:−
818:τ
805:−
792:×
780:−
411:τ
297:dimension
202:etabolism
180:bsorption
161:iberation
83:cosmetics
51:kinetikos
47:pharmakon
7167:Pharmacy
7143:22360418
7088:Category
6815:Pharmacy
6774:Pharmacy
6508:genetics
6480:Pharmacy
6467:Medicine
6277:Affinity
6236:Efficacy
6174:Analysis
6156:Toxicity
5803:USC*PACK
5768:Pmetrics
5614:RapidNCA
5594:Kinetica
5548:Software
5525:May 2016
5391:21366215
5309:16353916
5260:41194071
5217:28622472
5174:26015026
5028:13612670
5020:16787157
4985:20981028
4934:Phys.org
4922:20186894
4768:32119385
4736:32119385
4677:17630642
4617:98275795
4527:Pharmacy
4465:See also
4231:Amikacin
4006:Analysis
3299:figure).
2974:at time
2787:molecule
2744:Modeling
2401:Unitless
1981:integral
320:Formula
261:kinetics
246:ADME-Tox
229:xcretion
220:enzymes)
212:such as
69:such as
7134:3391520
7068:History
6781:General
6418:Related
6361:(L)ADME
6315:Initial
6299:Metrics
6246:Potency
6229:Metrics
6131:Binding
6101:Binding
5969:Agonist
5898:Uppsala
5894:Beijing
5874:Florida
5870:Buffalo
5787:Monolix
5760:WinBUGS
5715:Cloe PK
5687:SAAM II
5650:for R,
5644:WinSAAM
5582:PumasCP
5503:Please
5495:use of
5371:Bibcode
5300:2750974
5098:3977076
5063:3789400
4963:Bibcode
4178:Digoxin
4043:with a
3679:is the
3100:kidneys
3089:barrier
3019:initial
2960:initial
2793:(pKa),
314:Symbol
279:Metrics
210:enzymes
7141:
7131:
6848:&
6420:fields
5882:Leiden
5849:COPASI
5791:NONMEM
5770:for R.
5764:PKBugs
5735:Simcyp
5727:PK-Sim
5632:Boomer
5389:
5348:
5307:
5297:
5258:
5252:466923
5250:
5215:
5209:925881
5207:
5172:
5096:
5061:
5026:
5018:
4983:
4920:
4886:
4859:
4810:
4766:
4734:
4675:
4638:
4615:
4457:, the
4359:as an
3848:where
3785:where
3675:where
2717:41.8%
2641:where
1196:plasma
624:trough
325:value
99:dosing
42:(from
35:hours.
6617:Other
6354:LADME
5886:Otago
5857:MEGen
5845:Pumas
5775:Pumas
5711:acslX
5707:Pumas
5701:MCSim
5659:Pumas
5648:PKfit
5628:ADAPT
5576:Julia
5256:S2CID
5213:S2CID
5126:4 May
5116:(PDF)
5024:S2CID
4702:(PDF)
4695:(PDF)
4613:S2CID
4041:LC-MS
3280:curve
3096:liver
3076:brain
317:Unit
289:molar
285:moles
250:ADMET
233:drugs
169:IVIVC
114:IUPAC
7139:PMID
6968:shop
6920:List
6506:and
6430:and
6266:TD50
6262:LD50
6258:ED50
6254:IC50
6250:EC50
6052:Drug
5602:PKMP
5586:MLAB
5574:for
5566:for
5562:and
5560:bear
5387:PMID
5346:ISBN
5305:PMID
5248:PMID
5205:PMID
5170:PMID
5128:2013
5094:PMID
5059:PMID
5016:PMID
4981:PMID
4918:PMID
4884:ISBN
4857:ISBN
4808:ISBN
4764:PMID
4732:PMID
4673:PMID
4636:ISBN
3604:dose
3565:dose
3348:and
3273:PBPK
3098:and
2945:dose
2847:and
2797:and
2736:=AUC
2488:0.8
1979:The
331:Dose
147:ADME
141:ADME
7129:PMC
7121:doi
6363:: (
5825:Lyv
5638:),
5636:GUI
5511:or
5379:doi
5295:PMC
5287:doi
5240:doi
5197:doi
5160:hdl
5152:doi
5086:doi
5051:doi
5008:doi
4971:doi
4910:doi
4665:doi
4603:doi
4451:WHO
4449:or
4447:EPA
4410:.
3966:log
2732:AUC
2594:min
2571:max
2559:100
642:min
568:max
551:max
478:max
248:or
216:or
123::
7158::
7137:.
7127:.
7117:73
7115:.
7111:.
6264:,
6260:,
6256:,
6252:,
6213:,
6209:,
6133:,
5912:.
5904:,
5900:,
5892:,
5888:,
5884:,
5880:,
5876:,
5872:,
5855:,
5851:,
5847:,
5827:,
5809:,
5805:,
5797:,
5793:,
5789:,
5785:,
5777:,
5766:,
5744:,
5737:,
5733:,
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