565:
542:
40:
1013:
915:
31:
1753:
260:
739:
on 18 February 2016. In
February 2019, lesinurad was discontinued in the United States by its manufacturer for business reasons, and was subsequently withdrawn in Europe in July 2020.
215:
1453:
1396:
120:
654:
898:
of uric acid in the kidneys. This leads to increased uric acid excretion with the urine, and consequently lower blood levels. It also inhibits the protein
1359:
1289:
873:
and related drugs reduce the effectiveness of other anti-gout medications. It is not known conclusively whether this also applies to lesinurad, but
171:
1778:
1150:
838:. Some drugs that are metabolized by this enzyme have been shown to be slightly less effective when combined with lesinurad, examples including
811:
occurred in 2.1% of placebo patients, in 1.2% of patients with the therapeutic standard dose, and in 3.5% of patients with the double dose. For
767:) associated with gout. It is approved only for patients who have not achieved target uric acid levels with a xanthine oxidase inhibitor alone.
1236:
640:
1707:
1667:
1446:
674:
96:
934:
concentrations are reached after one to four hours. When in the bloodstream, the substance is almost completely (>98%) bound to
803:(an important marker for kidney function) was elevated in 4.3 to 7.8% of patients depending on the dose, as compared to 2.3% under
1062:
682:
InChI=1S/C17H14BrN3O2S/c18-16-19-20-17(24-9-15(22)23)21(16)14-8-7-11(10-5-6-10)12-3-1-2-4-13(12)14/h1-4,7-8,10H,5-6,9H2,(H,22,23)
819:
359:
245:
152:
1093:
1793:
1439:
1743:
1004:
are exposed to lesinurad concentrations that are about 1.8-fold higher than those with a normal function of this enzyme.
923:
859:
461:
1724:
521:
188:
1561:
748:
1788:
1366:
1296:
1243:
166:
780:
1813:
1773:
1712:
199:
560:
301:
1167:
1798:
1041:
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992:
of about five hours. Of the excreted dose, 30% are unchanged lesinurad, and the rest are metabolites.
818:
Other common side effects were influenza (5.1% vs. 2.7% under placebo), headache (5.3% vs. 4.1%), and
1783:
989:
858:), as well as in people who have genetically determined low CYP2C9 activity. The same may be true of
537:
328:
1803:
732:
376:
39:
1808:
1638:
1400:
1341:
850:. On the other hand, lesinurad concentrations in the blood are decreased by drugs that induce
784:
705:
510:
450:
273:
207:
110:
1128:
1331:
1323:
1193:
1001:
874:
823:
800:
577:
385:
283:
57:
470:
1757:
1570:
974:
807:. Manifest kidney problems were less frequent under the standard dose than under placebo:
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311:
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1063:"Prescription medicines: registration of new chemical entities in Australia, 2016"
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1021:
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138:
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Lesinurad is quickly and practically completely absorbed from the gut. Highest
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1604:
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1583:
1522:
1491:
1476:
958:
756:
725:
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441:
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946:
783:(juvenile gout), as well as severe impairment of kidney function, including
760:
341:
124:
1404:
1345:
1272:
1094:"Zurampic (lesinurad) Tablets, for Oral Use. Full Prescribing Information"
22:
1618:
1609:
1547:
903:
843:
717:
421:
183:
430:
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1310:
Wang J, Zeng W, Li S, Shen L, Gu Z, Zhang Y, et al. (March 2017).
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30:
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847:
835:
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988:
Lesinurad is excreted via the urine (63%) and feces (32%), with a
918:
The main metabolic pathways in humans. Involved enzymes are 2C9 =
913:
891:
639:
630:
501:
316:
1463:
962:
899:
713:
481:
161:
1435:
945:
It is metabolized mainly by the liver enzyme CYP2C9 to various
267:
178:
854:
and increased by substances that inhibit this enzyme (such as
170:
1389:. In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.).
1099:. AstraZeneca AB, S-151 85 Sodertalje, Sweden. Archived from
526:
78:
1312:"Discovery and Assessment of Atropisomers of (±)-Lesinurad"
254:
63:
1171:
815:, the frequencies were 1.7%, 0.6% and 2.5%, respectively.
84:
72:
973:
and CYP3A only play minor roles in its metabolization.
735:
granted a marketing authorisation valid throughout the
965:
M4 by microsomal epoxide hydrolase (mEH). The enzymes
1741:
97:
75:
69:
1020:
Lesinurad is a white to off-white powder and is not
834:
The substance is a mild inducer of the liver enzyme
87:
81:
60:
1655:
1637:
1597:
1569:
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1484:
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1131:. US Food and Drug Administration. 22 December 2015
902:, which is associated with hyperuricemia caused by
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731:It received FDA approval on 22 December 2015. The
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1397:National Center for Biotechnology Information
759:, for treating hyperuricemia (high levels of
16:Pharmaceutical drug for the treatment of gout
8:
187:
21:
1360:"Zurampic: EPAR – Public assessment report"
1290:"Zurampic: EPAR – Public assessment report"
1267:
1265:
1263:
1261:
1259:
1257:
1255:
1253:
775:The drug is contraindicated in people with
728:when these medications are not sufficient.
1566:
1481:
1454:
1440:
1432:
1170:. Ironwood Pharmaceuticals. Archived from
1123:
1121:
662:c1ccc2c(c1)c(ccc2n3c(nnc3Br)SCC(=O)O)C4CC4
563:
540:
449:
1335:
877:does not negatively affect its activity.
469:
747:Lesinurad is used in combination with a
1748:
1387:"Lesinurad Therapy and CYP2C9 Genotype"
1200:. The European Union. 17 September 2018
1054:
679:
659:
536:
429:
364:
143:
1299:. 9 March 2016. pp. 18–19, 38–39.
1237:"Zurampic: EPAR – Product Information"
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1067:Therapeutic Goods Administration (TGA)
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20:
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846:. It might also be a mild inducer of
509:
129:
7:
1427:. U.S. National Library of Medicine.
1088:
1086:
1084:
894:, a protein that is responsible for
227:
489:
400:
1276:: Zurampic. Accessed 19 July 2017.
14:
1273:FDA Professional Drug Information
1751:
826:reactions were rare (<0.1%).
597:
588:
56:
38:
29:
1316:ACS Medicinal Chemistry Letters
1129:"Drug Trial Snapshot: Zurampic"
1044:, a fixed-dose combination drug
820:gastroesophageal reflux disease
716:. It is recommended only as an
687:Key:FGQFOYHRJSUHMR-UHFFFAOYSA-N
594:
1779:Drugs developed by AstraZeneca
1328:10.1021/acsmedchemlett.6b00465
1016:Two atropisomers of lesinurad.
609:
603:
582:
1:
1151:"EPAR summary for the public"
957:, M3c. The latter is quickly
949:products, predominantly to a
924:microsomal epoxide hydrolase
860:microsomal epoxide hydrolase
1562:Xanthine oxidase inhibitors
953:substance called M3 and an
710:high blood uric acid levels
1830:
1407:. Bookshelf ID: NBK537366.
1392:Medical Genetics Summaries
1369:. 9 March 2016. p. 9.
749:xanthine oxidase inhibitor
572:Chemical and physical data
1702:
1367:European Medicines Agency
1297:European Medicines Agency
1244:European Medicines Agency
1198:European Medicines Agency
670:
650:
355:
37:
28:
985:has also been detected.
346:Urine (63%), feces (32%)
1425:Drug Information Portal
708:inhibitor for treating
367:2-{sulfanyl}acetic acid
1168:"Duzallo and Zurampic"
1017:
1000:People who are CYP2C9
927:
795:Adverse drug reactions
1794:Cyclopropyl compounds
1156:. EMA. 13 March 2016.
1042:Lesinurad/allopurinol
1015:
917:
777:tumour lysis syndrome
990:biological half-life
862:inhibitors (such as
799:In clinical trials,
781:Lesch–Nyhan syndrome
1106:on 24 December 2015
890:Lesinurad inhibits
886:Mechanism of action
733:European Commission
263:(Prescription only)
25:
1729:Never to phase III
1639:Mitotic inhibitors
1018:
928:
1739:
1738:
1633:
1632:
1556:
1555:
1174:on 10 August 2020
1002:poor metabolizers
822:(2.7% vs. 0.8%).
785:kidney transplant
771:Contraindications
706:urate transporter
695:
694:
641:Interactive image
522:CompTox Dashboard
271:
258:
181:
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1789:Carboxylic acids
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1571:purine analogues
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910:Pharmacokinetics
875:low dose aspirin
824:Hypersensitivity
801:serum creatinine
712:associated with
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1462:Drugs used for
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1385:Dean L (2019).
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1378:Further reading
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975:Glucuronidation
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302:Protein binding
292:Bioavailability
284:Pharmacokinetic
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1497:Sulfinpyrazone
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1414:External links
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1322:(3): 299–303.
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1246:. 6 July 2017.
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1069:. 21 June 2022
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1024:. It is a 1:1
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1684:Urate oxidase
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197:
190:
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114:
112:
108:
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103:
92:
54:
52:Pronunciation
50:
47:Clinical data
45:
41:
36:
32:
27:
19:
1799:Naphthalenes
1670:
1625:Topiroxostat
1619:Myo-inositol
1542:
1528:Atorvastatin
1424:
1391:
1354:
1319:
1315:
1305:
1202:. Retrieved
1197:
1188:
1176:. Retrieved
1172:the original
1162:
1145:
1133:. Retrieved
1108:. Retrieved
1101:the original
1071:. Retrieved
1066:
1057:
1030:atropisomers
1019:
999:
987:
951:hydroxylated
944:
932:blood plasma
929:
896:reabsorption
889:
881:Pharmacology
868:
833:
830:Interactions
817:
798:
789:hemodialysis
774:
746:
743:Medical uses
730:
720:with either
701:
700:(brand name
697:
696:
329:Elimination
246:Legal status
240:Legal status
153:License data
18:
1784:Bromoarenes
1715:from market
1693:Pegloticase
1688:Rasburicase
1614:Phytic acid
1579:Allopurinol
1538:Guaifenesin
1533:Fenofibrate
1477:Uricosurics
1421:"Lesinurad"
1110:23 December
1028:mixture of
1022:hygroscopic
856:fluconazole
840:simvastatin
765:blood serum
753:allopurinol
722:allopurinol
624: g·mol
561:100.216.089
511:CHEBI:90929
386:878672-00-5
351:Identifiers
139:MedlinePlus
111:Trade names
1804:Thioethers
1768:Categories
1663:Cinchophen
1647:Colchicine
1605:Febuxostat
1589:Tisopurine
1584:Oxypurinol
1523:Amlodipine
1492:Probenecid
1135:14 October
1049:References
959:hydrolyzed
922:and mEH =
869:High dose
791:patients.
757:febuxostat
751:, such as
726:febuxostat
629:3D model (
617:Molar mass
471:09ERP08I3W
442:ChemSpider
377:CAS Number
360:IUPAC name
312:Metabolism
1809:Triazoles
1725:Phase III
1713:Withdrawn
1679:Sevelamer
1610:Inositols
1543:Lesinurad
1516:secondary
1204:2 October
1194:"Duzallo"
1008:Chemistry
947:oxidation
938:, mainly
761:uric acid
698:Lesinurad
342:Excretion
331:half-life
200:Routes of
189:Lesinurad
131:Monograph
125:Drugs.com
23:Lesinurad
1758:Medicine
1548:Losartan
1405:30742400
1399:(NCBI).
1346:28337320
1073:10 April
1036:See also
904:diuretic
844:warfarin
718:adjuvant
702:Zurampic
451:28527877
422:DrugBank
411:56928182
336:~5 hours
216:ATC code
184:DailyMed
115:Zurampic
1674:aspirin
1485:primary
1337:5346995
1178:31 July
1026:racemic
971:CYP2C19
961:to the
955:epoxide
940:albumin
906:drugs.
871:aspirin
805:placebo
763:in the
704:) is a
578:Formula
431:DB11560
397:PubChem
317:Hepatic
306:>98%
232:)
226: (
224:M04AB05
208:tablets
186::
169::
145:a616015
102:-ew-rad
1744:Portal
1708:WHO-EM
1671:except
1668:NSAIDs
1403:
1344:
1334:
983:UGT2B7
979:UGT1A1
967:CYP1A1
920:CYP2C9
852:CYP2C9
848:CYP2B6
836:CYP3A4
655:SMILES
622:404.28
491:D09921
321:CYP2C9
274:℞-only
272:
259:
206:Oral (
182:
172:by INN
165:
105:
1656:Other
1598:other
1363:(PDF)
1293:(PDF)
1240:(PDF)
1154:(PDF)
1104:(PDF)
1097:(PDF)
892:URAT1
675:InChI
631:JSmol
502:ChEBI
296:~100%
1464:gout
1401:PMID
1342:PMID
1206:2020
1180:2020
1137:2018
1112:2015
1075:2023
981:and
963:diol
900:OAT4
842:and
787:and
714:gout
482:KEGG
462:UNII
286:data
121:AHFS
1468:M04
1332:PMC
1324:doi
866:).
779:or
755:or
724:or
527:EPA
401:CID
229:WHO
167:EMA
100:SIN
98:le-
79:juː
1770::
1721::
1423:.
1395:.
1365:.
1340:.
1330:.
1318:.
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1295:.
1281:^
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1214:^
1196:.
1120:^
1083:^
1065:.
1032:.
969:,
942:.
595:Br
592:14
586:17
268:US
261:S4
255:AU
179:US
162:EU
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