Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors. NLM AIDSLINE Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors.

Drug Metab Dispos. 1998 Mar;26(3):257-60. Unique Identifier : AIDSLINE MED/98160431
Iribarne C; Berthou F; Carlhant D; Dreano Y; Picart D; Lohezic F; Riche C; Laboratoires de Biochimie-Nutrition EA948, Faculte de Medecine, Brest,; France.

Abstract: Ritonavir, indinavir, and saquinavir, all human immunodeficiency virus-1 protease inhibitors with a potent antiviral effect during triple therapy, are extensively metabolized by liver cytochrome P450 3A4. As this P450 isoform is involved in the metabolism of about 50% of drugs, coadministration of protease inhibitors with other drugs may lead to serious effects due to enzyme inhibition. Among these drugs, methadone and buprenorphine, both metabolized by P450 3A4, are potential candidates to drug interactions. In this study, metabolic interactions between these protease inhibitors and methadone or buprenorphine were studied in vitro in a panel of 13 human liver microsomes. Ritonavir was the most potent competitive inhibitor with Ki about 50 and 20 nM for methadone and buprenorphine metabolisms, respectively. Indinavir and saquinavir also inhibited methadone N-demethylation (Ki about 3 and 15 microM, respectively) and buprenorphine N-dealkylation Ki about 0.8 and 7 microM, respectively). The rank order of inhibition potency against metabolism of methadone and buprenorphine was ritonavir > indinavir > saquinavir. There is obvious potential for clinically significant drug interactions, particularly with ritonavir. In brief, caution should be advised if human immunodeficiency virus-1 protease inhibitors are coadministered with methadone and buprenorphine.
Keywords: *Buprenorphine/METABOLISM *HIV Protease Inhibitors/PHARMACOLOGY *Methadone/METABOLISMKWDbuprenorphine/metabolismKWDhivproteaseinhibitors/pharmacologyKWDmethadone/metabolism
980630
M9861780

Copyright © 1998 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .