Interactions between buprenorphine and the protease inhibitors darunavir-ritonavir and fosamprenavir-ritonavir.

Abstract

BACKGROUND:

This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir.

METHODS:

The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphine-naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir) before and after 15 days of PI administration. PI pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and an equal number of sex-, age-, race-, and weight-matched, healthy, non-opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not buprenorphine.

RESULTS:

There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine.

CONCLUSIONS:

Dose adjustments are not likely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadministered for the treatment of opioid dependence and HIV disease.

• Authors: Valerie A Gruber, Petrie M Rainey, David E Moody, Gene D Morse, Qing Ma, Sudha Prathikanti, Patricia A Pade, Anika A H Alvanzo, Elinore F McCance-Katz
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 54 Issue 3 Pg. 414-23 (Feb 01 2012) ISSN: 1537-6591 [Electronic] United States
• PMID: 22100576 (Publication Type: Controlled Clinical Trial, Historical Article, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-HIV Agents
• Carbamates
• Furans
• Narcotic Antagonists
• Organophosphates
• Protease Inhibitors
• Sulfonamides
• buprenorphine-3-O-glucuronide
• Naloxone
• Buprenorphine
• norbuprenorphine
• Ritonavir
• fosamprenavir
• Darunavir

Topics

• Anti-HIV Agents (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Buprenorphine (administration & dosage, analogs & derivatives, blood, pharmacokinetics)
• Carbamates (administration & dosage, blood, pharmacokinetics)
• Darunavir
• Drug Interactions
• Female
• Furans
• Half-Life
• History, 16th Century
• History, 17th Century
• Humans
• Male
• Naloxone (pharmacology)
• Narcotic Antagonists (administration & dosage, pharmacokinetics)
• Opiate Substitution Treatment
• Organophosphates (administration & dosage, blood, pharmacokinetics)
• Protease Inhibitors (administration & dosage, blood, pharmacokinetics)
• Ritonavir (administration & dosage, blood, pharmacokinetics)
• Sulfonamides (administration & dosage, blood, pharmacokinetics)