![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 27, Issue 8, 895-901, August 1999
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.
This article has been cited by other articles:
|
|
 |
|
  A. M. Cammett, T. R. MacGregor, J. M. Wruck, F. Felizarta, P. Miailhes, J. Mallolas, and P. J. Piliero Pharmacokinetic Assessment of Nevirapine and Metabolites in Human Immunodeficiency Virus Type 1-Infected Patients with Hepatic Fibrosis Antimicrob. Agents Chemother., October 1, 2009; 53(10): 4147 - 4152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
 |
 |
 |
|
 |
 |
 |
