DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riska, P.
Right arrow Articles by Keirns, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riska, P.
Right arrow Articles by Keirns, J.

Vol. 27, Issue 8, 895-901, August 1999

Disposition and Biotransformation of the Antiretroviral Drug Nevirapine in Humans

Paul Riska, Michael Lamson, Thomas MacGregor, John Sabo, Susan Hattox, Joseph Pav, and James Keirns

Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut

The pharmacokinetics and biotransformation of the antiretroviral agent nevirapine (NVP) after autoinduction were characterized in eight healthy male volunteers. Subjects received 200-mg NVP tablets once daily for 2 weeks, followed by 200 mg twice daily for 2 weeks. Then they received a single oral dose (solution) of 50 mg containing 100 µCi of [14C]NVP. Biological fluids were analyzed for total radioactivity, parent compound (HPLC/UV), and metabolites (electrospray liquid chromatography/mass spectroscopy and liquid chromatography/tandem mass spectroscopy). Mean recovery of radioactivity was 91.4%, with 81.3% excreted in urine and 10.1% recovered in the feces over a period of 10 days. Circulating radioactivity was evenly distributed between whole blood and plasma. At maximum plasma concentration, parent compound accounted for ~75% of the circulating radioactivity. Mean plasma elimination half-lives for total radioactivity and NVP were 21.3 and 20.0 h, respectively. Several metabolites were identified in urine including 2-hydroxynevirapine glucuronide (18.6%), 3-hydroxynevirapine glucuronide (25.7%), 12-hydroxynevirapine glucuronide (23.7%), 8-hydroxynevirapine glucuronide (1.3%), 3-hydroxynevirapine (1.2%), 12-hydroxynevirapine (0.6%), and 4-carboxynevirapine (2.4%). Greater than 80% of the radioactivity in urine was made up of glucuronidated conjugates of hydroxylated metabolites of NVP. Thus, cytochrome P-450 metabolism, glucuronide conjugation, and urinary excretion of glucuronidated metabolites represent the primary route of NVP biotransformation and elimination in humans. Only a small fraction of the dose (2.7%) was excreted in urine as parent compound.

Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
B. Wen, Y. Chen, and W. L. Fitch
Metabolic Activation of Nevirapine in Human Liver Microsomes: Dehydrogenation and Inactivation of Cytochrome P450 3A4
Drug Metab. Dispos., July 1, 2009; 37(7): 1557 - 1562.
[Abstract] [Full Text] [PDF]

Home page
 Int J STD AIDSHome page
T W Mahungu, M A Johnson, A Owen, and D J Back
The impact of pharmacogenetics on HIV therapy
Int J STD AIDS, March 1, 2009; 20(3): 145 - 151.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
H. Stocker, G. Kruse, P. Kreckel, C. Herzmann, K. Arasteh, J. Claus, H. Jessen, C. Cordes, B. Hintsche, F. Schlote, et al.
Nevirapine Significantly Reduces the Levels of Racemic Methadone and (R)-Methadone in Human Immunodeficiency Virus-Infected Patients
Antimicrob. Agents Chemother., November 1, 2004; 48(11): 4148 - 4153.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. Azoulay, M.-C. Nevers, C. Creminon, L. Heripret, J. Durant, P. Dellamonica, J. Grassi, R. Guedj, and D. Duval
Sensitive Enzyme Immunoassay for Measuring Plasma and Intracellular Nevirapine Levels in Human Immunodeficiency Virus-Infected Patients
Antimicrob. Agents Chemother., January 1, 2004; 48(1): 104 - 109.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Spatzenegger, H. Liu, Q. Wang, A. Debarber, D. R. Koop, and J. R. Halpert
Analysis of Differential Substrate Selectivities of CYP2B6 and CYP2E1 by Site-Directed Mutagenesis and Molecular Modeling
J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 477 - 487.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
K. L. Tuck, M. P. Freeman, P. J. Hayball, G. L. Stretch, and I. Stupans
The In Vivo Fate of Hydroxytyrosol and Tyrosol, Antioxidant Phenolic Constituents of Olive Oil, after Intravenous and Oral Dosing of Labeled Compounds to Rats
J. Nutr., July 1, 2001; 131(7): 1993 - 1996.
[Abstract] [Full Text] [PDF]

Home page
 Sex. Transm. Infect.Home page
M G. Brook and R. F Miller
HIV associated nephropathy: a treatable condition
Sex Transm Inf, April 1, 2001; 77(2): 97 - 100.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
H. Izzedine, V. Launay-Vacher, G. Aymard, M. Legrand, and G. Deray
Pharmacokinetic of nevirapine in haemodialysis
Nephrol. Dial. Transplant., January 1, 2001; 16(1): 192 - 193.
[Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. R. Faucette, R. L. Hawke, E. L. Lecluyse, S. S. Shord, B. Yan, R. M. Laethem, and C. M. Lindley
Validation of Bupropion Hydroxylation as a Selective Marker of Human Cytochrome P450 2B6 Catalytic Activity
Drug Metab. Dispos., October 1, 2000; 28(10): 1222 - 1230.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
P. S. Riska, D. P. Joseph, R. M. Dinallo, W. C. Davidson, J. J. Keirns, and S. E. Hattox
Biotransformation of Nevirapine, a Non-nucleoside HIV-1 Reverse Transcriptase Inhibitor, in Mice, Rats, Rabbits, Dogs, Monkeys, and Chimpanzees
Drug Metab. Dispos., December 1, 1999; 27(12): 1434 - 1447.
[Abstract] [Full Text]

Home page
 Drug Metab. Dispos.Home page
D. A. Erickson, G. Mather, W. F. Trager, R. H. Levy, and J. J. Keirns
Characterization of the In Vitro Biotransformation of the HIV-1 Reverse Transcriptase Inhibitor Nevirapine by Human Hepatic Cytochromes P-450
Drug Metab. Dispos., December 1, 1999; 27(12): 1488 - 1495.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.