title: 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.affiliation: Department of Psychiatry, University of California San Francisco, CA, USA. valerie.gruber@ucsf.edu
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Gruber
authors.forename: Petrie M
authors.initials: PM
authors.lastname: Rainey
authors.forename: David E
authors.initials: DE
authors.lastname: Moody
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Sudha
authors.initials: S
authors.lastname: Prathikanti
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Pade
authors.forename: Anika A H
authors.initials: AA
authors.lastname: Alvanzo
authors.forename: Elinore F
authors.initials: EF
authors.lastname: McCance-Katz
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D002219:Carbamates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D005663:Furans; D006207:Half-Life; D049669:History, 16th Century; D049670:History, 17th Century; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D058850:Opiate Substitution Treatment; D010755:Organophosphates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D009292:Narcotic Antagonists; D010755:Organophosphates; D011480:Protease Inhibitors; D013449:Sulfonamides; C050182:buprenorphine-3-O-glucuronide; D009270:Naloxone; D002047:Buprenorphine; C043585:norbuprenorphine; D019438:Ritonavir; C426859:fosamprenavir; D000069454:Darunavir
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