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Pathway Description
Nevirapine Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Nevirapine is used in the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to the tyrosines at amino acid residues 181 and 188 of HIV-1 reverse transcriptase. Nevirapine is metabolized in the liver to 2-, 3-, 8-, and 12-hydroxynevirapine by the induction of CYP enzymes, mainly CYP3A4 and CYP2B6. 12-hydroxynevirapine may be further oxidated by ALDH to form 4-carboxynevirapine. These hydroxyl metabolites are glucuronidated by UDP glucuronosyl transferases (UGTs), then exit the cell via the adenosine triphosphate-binding cassette gene ABCC10 for urinary excretion.
References
Nevirapine Pathway References
[PharmgKB](http://www.pharmgkb.org/pathway/PA165950411)
Wen B, Chen Y, Fitch WL: Metabolic activation of nevirapine in human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. Drug Metab Dispos. 2009 Jul;37(7):1557-62. doi: 10.1124/dmd.108.024851. Epub 2009 Apr 13.
Pubmed: 19364830
Chen J, Mannargudi BM, Xu L, Uetrecht J: Demonstration of the metabolic pathway responsible for nevirapine-induced skin rash. Chem Res Toxicol. 2008 Sep;21(9):1862-70. doi: 10.1021/tx800177k. Epub 2008 Aug 26.
Pubmed: 18729332
Riska P, Lamson M, MacGregor T, Sabo J, Hattox S, Pav J, Keirns J: Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos. 1999 Aug;27(8):895-901.
Pubmed: 10421616
Liptrott NJ, Pushpakom S, Wyen C, Fatkenheuer G, Hoffmann C, Mauss S, Knechten H, Brockmeyer NH, Hopper-Borge E, Siccardi M, Back DJ, Khoo SH, Pirmohamed M, Owen A: Association of ABCC10 polymorphisms with nevirapine plasma concentrations in the German Competence Network for HIV/AIDS. Pharmacogenet Genomics. 2012 Jan;22(1):10-9. doi: 10.1097/FPC.0b013e32834dd82e.
Pubmed: 22082652
Cheeseman SH, Hattox SE, McLaughlin MM, Koup RA, Andrews C, Bova CA, Pav JW, Roy T, Sullivan JL, Keirns JJ: Pharmacokinetics of nevirapine: initial single-rising-dose study in humans. Antimicrob Agents Chemother. 1993 Feb;37(2):178-82.
Pubmed: 8452345
Havlir D, Cheeseman SH, McLaughlin M, Murphy R, Erice A, Spector SA, Greenough TC, Sullivan JL, Hall D, Myers M, et al.: High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection. J Infect Dis. 1995 Mar;171(3):537-45.
Pubmed: 7533197
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