Interactions Between Buprenorphine and the Protease Inhibitors Darunavir-Ritonavir and Fosamprenavir-Ritonavir

• Published in: Clinical infectious diseases Vol. 54; no. 3; pp. 414 - 423
• Main Authors: Gruber, Valerie A., Rainey, Petrie M., Moody, David E., Morse, Gene D., Ma, Qing, Prathikanti, Sudha, Pade, Patricia A., Alvanzo, Anika A. H., McCance-Katz, Elinore F.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2012
• Subjects: Anti-HIV Agents - administration & dosage; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Area Under Curve; Biological and medical sciences; Buprenorphine - administration & dosage; Buprenorphine - analogs & derivatives; Buprenorphine - blood; Buprenorphine - pharmacokinetics; Carbamates - administration & dosage; Carbamates - blood; Carbamates - pharmacokinetics; Darunavir; Data ranges; Dosage; Drug Interactions; Female; Half-Life; History, 16th Century; History, 17th Century; HIV; HIV/AIDS; Human immunodeficiency virus; Humans; Infectious diseases; Male; Medical sciences; Medications; Memory interference; Metabolites; Methadone; Naloxone - pharmacology; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - pharmacokinetics; Opiate Substitution Treatment; Opioid analgesics; Organophosphates - administration & dosage; Organophosphates - blood; Organophosphates - pharmacokinetics; Pain management; Pharmacokinetics; Pharmacology. Drug treatments; Protease inhibitors; Protease Inhibitors - administration & dosage; Protease Inhibitors - blood; Protease Inhibitors - pharmacokinetics; Ritonavir - administration & dosage; Ritonavir - blood; Ritonavir - pharmacokinetics; Statistical median; Substance abuse treatment; Sulfonamides - administration & dosage; Sulfonamides - blood; Sulfonamides - pharmacokinetics; Antiretroviral agent; Darunavir; Enzyme; Ritonavir; Enzyme inhibitor; Non peptide compound; Opiates; Narcotic analgesic; Infection; Peptidases; Fosamprenavir; Buprenorphine; Hydrolases; Antiviral; Protease inhibitor
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cir799

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.