641:"FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF VEKLURY® (remdesivir) FOR THE TREATMENT OF CORONAVIRUS DISEASE 2019 (COVID-19) IN PEDIATRIC PATIENTS WEIGHING 3.5 KG TO LESS THAN 40 KG OR PEDIATRIC PATIENTS LESS THAN 12 YEARS OF AGE WEIGHING AT LEAST 3.5 KG, WITH POSITIVE RESULTS OF DIRECT SARS-CoV-2 VIRAL TESTING WHO ARE: HOSPITALIZED, OR NOT HOSPITALIZED AND HAVE MILD-TO-MODERATE COVID-19, AND ARE AT HIGH RISK FOR PROGRESSION TO SEVERE COVID-19, INCLUDING HOSPITALIZATION OR DEATH"
140:
43:
171:
before it reaches the site of action or systemic circulation. The effect is most associated with orally administered medications, but some drugs still undergo first-pass metabolism even when delivered via an alternate route (e.g., IV, IM, etc.). During this metabolism, drug is lost during the process
365:
dose. There is marked individual variation in the oral dose due to differences in the extent of first pass metabolism, frequently among several other factors. Oral bioavailability of many vulnerable drugs appears to be increased in patients with compromised liver function. Bioavailability is also
294:). For this reason, remdesivir is administered by IV infusion, bypassing the portal vein. However, significant hepatic extraction still occurs because of second pass metabolism, whereby a fraction of venous blood travels through the hepatic portal vein and hepatocytes.
176:
and gut wall. The liver is the major site of first pass effect; however, it can also occur in the lungs, vasculature or other metabolically active tissues in the body. Notable drugs that experience a significant first-pass effect are
290:. Remdesivir cannot be administered orally because the entire dose would be trapped in the liver with little achieving systemic circulation or reaching target organs and cells (for example, cells infected with
569:
393:
543:
689:
Herman TF, Santos C. First Pass Effect. 2022 Sep 24. In: StatPearls . Treasure Island (FL): StatPearls
Publishing; 2022 Jan–. PMID 31869143.
60:
126:
680:
268:
107:
79:
64:
86:
707:
669:
644:
366:
increased if another drug competing for first pass metabolism enzymes is given concurrently (e.g., propranolol and
93:
53:
702:
75:
286:
An example of a drug where first pass metabolism is a complication and disadvantage is in the antiviral drug
327:
323:
403:
302:
523:
229:(THC). First-pass metabolism is not to be confused with Phase I metabolism, which is a separate process.
565:
408:
252:
355:
343:
226:
202:
361:
Drugs with high first pass effect typically have a considerably higher oral dose than sublingual or
256:
139:
504:
272:
100:
622:
539:
496:
488:
453:
445:
428:
Rowland, Malcolm (January 1972). "Influence of route of administration on drug availability".
347:
31:
612:
604:
531:
480:
437:
383:
248:
237:
684:
305:
280:
160:
354:, avoid the first-pass effect because they allow drugs to be absorbed directly into the
617:
592:
535:
367:
194:
182:
677:
593:"Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment"
696:
484:
339:
233:
178:
164:
17:
508:
608:
387:
316:
335:
331:
312:
222:
42:
362:
351:
291:
287:
264:
198:
186:
168:
492:
449:
297:
The four primary systems that affect the first pass effect of a drug are the
640:
218:
210:
206:
626:
471:
Pond, Susan M.; Tozer, Thomas N. (January 1984). "First-Pass
Elimination".
441:
500:
457:
232:
First pass metabolism may occur in the liver (for propranolol, lidocaine,
319:
but fail on first-pass metabolism because it is biochemically selective.
214:
190:
241:
298:
163:
at a specific location in the body which leads to a reduction in the
267:
many drugs, sometimes to such an extent that only a small amount of
260:
173:
138:
528:
Encyclopedia of
Forensic Sciences, Third Edition (Third Edition)
398:
390:
standing for absorption, distribution, metabolism, and excretion
379:
36:
308:, gut wall enzymes, bacterial enzymes, and hepatic enzymes.
143:
Illustration showing the hepatic portal vein system
67:. Unsourced material may be challenged and removed.
263:before it reaches the rest of the body. The liver
247:After a drug is swallowed, it is absorbed by the
172:of absorption which is generally related to the
524:"Pharmacology and Mechanism of Action of Drugs"
279:through the liver thus may greatly reduce the
591:Yan, Victoria C.; Muller, Florian L. (2020).
8:
271:emerges from the liver to the rest of the
616:
127:Learn how and when to remove this message
564:Bath-Hextall, Fiona (October 16, 2013).
236:, and nitroglycerin) or in the gut (for
420:
530:, Oxford: Elsevier, pp. 144–154,
394:Biopharmaceutics Classification System
566:"Understanding First Pass Metabolism"
7:
65:adding citations to reliable sources
572:from the original on July 28, 2021
536:10.1016/b978-0-12-823677-2.00086-6
522:Carlin, Michelle G. (2023-01-01),
430:Journal of Pharmaceutical Sciences
25:
647:from the original on 12 May 2020
485:10.2165/00003088-198409010-00001
315:, drug candidates may have good
41:
597:ACS Medicinal Chemistry Letters
52:needs additional citations for
678:Influence of Route of Exposure
609:10.1021/acsmedchemlett.0c00316
1:
27:Phenomenon of drug metabolism
670:National Library of Medicine
568:. University of Nottingham.
255:. It is carried through the
724:
526:, in Houck, Max M. (ed.),
29:
473:Clinical Pharmacokinetics
324:routes of administration
30:Not to be confused with
442:10.1002/jps.2600610111
404:Enteral administration
157:presystemic metabolism
144:
409:Partition coefficient
253:hepatic portal system
159:) is a phenomenon of
153:first-pass metabolism
142:
18:First pass metabolism
356:systemic circulation
344:inhalational aerosol
227:tetrahydrocannabinol
197:(drinking alcohol),
61:improve this article
708:Medicinal chemistry
674:Toxicology Tutor II
76:"First pass effect"
683:2010-06-11 at the
273:circulatory system
145:
545:978-0-12-823678-9
149:first pass effect
137:
136:
129:
111:
32:First dose effect
16:(Redirected from
715:
703:Pharmacokinetics
657:
656:
654:
652:
637:
631:
630:
620:
603:(7): 1361–1366.
588:
582:
581:
579:
577:
561:
555:
554:
553:
552:
519:
513:
512:
468:
462:
461:
425:
384:pharmacokinetics
382:, an acronym in
303:gastrointestinal
249:digestive system
238:benzylpenicillin
132:
125:
121:
118:
112:
110:
69:
45:
37:
21:
723:
722:
718:
717:
716:
714:
713:
712:
693:
692:
685:Wayback Machine
666:
661:
660:
650:
648:
639:
638:
634:
590:
589:
585:
575:
573:
563:
562:
558:
550:
548:
546:
521:
520:
516:
470:
469:
465:
427:
426:
422:
417:
376:
281:bioavailability
251:and enters the
161:drug metabolism
151:(also known as
133:
122:
116:
113:
70:
68:
58:
46:
35:
28:
23:
22:
15:
12:
11:
5:
721:
719:
711:
710:
705:
695:
694:
691:
690:
687:
665:
664:External links
662:
659:
658:
632:
583:
556:
544:
514:
463:
419:
418:
416:
413:
412:
411:
406:
401:
396:
391:
375:
372:
368:chlorpromazine
183:chlorpromazine
167:of the active
135:
134:
49:
47:
40:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
720:
709:
706:
704:
701:
700:
698:
688:
686:
682:
679:
675:
671:
668:
667:
663:
646:
642:
636:
633:
628:
624:
619:
614:
610:
606:
602:
598:
594:
587:
584:
571:
567:
560:
557:
547:
541:
537:
533:
529:
525:
518:
515:
510:
506:
502:
498:
494:
490:
486:
482:
478:
474:
467:
464:
459:
455:
451:
447:
443:
439:
435:
431:
424:
421:
414:
410:
407:
405:
402:
400:
397:
395:
392:
389:
385:
381:
378:
377:
373:
371:
369:
364:
359:
357:
353:
349:
345:
341:
340:intramuscular
337:
333:
329:
325:
320:
318:
314:
309:
307:
304:
300:
295:
293:
289:
284:
283:of the drug.
282:
278:
274:
270:
266:
262:
258:
254:
250:
245:
243:
239:
235:
234:clomethiazole
230:
228:
224:
220:
216:
212:
208:
204:
200:
196:
192:
188:
184:
180:
179:buprenorphine
175:
170:
166:
165:concentration
162:
158:
154:
150:
141:
131:
128:
120:
117:December 2016
109:
106:
102:
99:
95:
92:
88:
85:
81:
78: –
77:
73:
72:Find sources:
66:
62:
56:
55:
50:This article
48:
44:
39:
38:
33:
19:
673:
649:. Retrieved
635:
600:
596:
586:
574:. Retrieved
559:
549:, retrieved
527:
517:
476:
472:
466:
436:(1): 70–74.
433:
429:
423:
388:pharmacology
360:
328:insufflation
322:Alternative
321:
317:druglikeness
310:
296:
285:
276:
246:
231:
156:
152:
148:
146:
123:
114:
104:
97:
90:
83:
71:
59:Please help
54:verification
51:
576:October 26,
479:(1): 1–25.
348:transdermal
336:intravenous
332:suppository
313:drug design
269:active drug
265:metabolizes
257:portal vein
223:propranolol
697:Categories
551:2024-01-17
415:References
363:parenteral
352:sublingual
326:, such as
292:SARS-CoV-2
288:remdesivir
277:first pass
199:imipramine
187:cimetidine
87:newspapers
493:0312-5963
450:0022-3549
259:into the
219:pethidine
211:midazolam
207:lidocaine
681:Archived
645:Archived
627:32665809
570:Archived
509:28006040
374:See also
215:morphine
191:diazepam
618:7315846
501:6362950
458:5019220
301:of the
299:enzymes
275:. This
242:insulin
203:insulin
195:ethanol
101:scholar
651:4 July
625:
615:
542:
507:
499:
491:
456:
448:
225:, and
103:
96:
89:
82:
74:
505:S2CID
350:, or
306:lumen
261:liver
174:liver
108:JSTOR
94:books
653:2024
623:PMID
578:2017
540:ISBN
497:PMID
489:ISSN
454:PMID
446:ISSN
399:Drug
386:and
380:ADME
240:and
169:drug
147:The
80:news
613:PMC
605:doi
532:doi
481:doi
438:doi
370:).
311:In
244:).
155:or
63:by
699::
676:,
672:,
643:.
621:.
611:.
601:11
599:.
595:.
538:,
503:.
495:.
487:.
475:.
452:.
444:.
434:61
432:.
358:.
346:,
342:,
338:,
334:,
330:,
221:,
217:,
213:,
209:,
205:,
201:,
193:,
189:,
185:,
181:,
655:.
629:.
607::
580:.
534::
511:.
483::
477:9
460:.
440::
130:)
124:(
119:)
115:(
105:·
98:·
91:·
84:·
57:.
34:.
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
