title: Pharmacokinetic interactions between buprenorphine/naloxone and raltegravir in subjects receiving chronic buprenorphine/naloxone treatment.
abstract: BACKGROUND
  Interactions between human immuno-deficiency virus (HIV) and opioid-dependence therapies can occur.
  
  
  OBJECTIVE
  We sought to determine whether such interactions occurred between buprenorphine/naloxone and raltegravir.
  
  
  METHODS
  We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 12 HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone therapy. Subjects underwent baseline and steady-state evaluation of the effect of raltegravir 400 mg BID on buprenorphine/naloxone parameters.
  
  
  RESULTS
  Compared with baseline values, buprenorphine AUC(0-24 h) (58.2 vs. 56.0 hr*ng/mL) and C(max) (7.37 vs. 6.60 ng/mL) did not differ significantly after achieving steady-state raltegravir. Similar analyses of norbuprenorphine, the primary metabolite of buprenorphine, demonstrated no significant difference after raltegravir administration. Naloxone concentrations were unchanged for AUC(0-24 h) (.595 vs. .581 hr*ng/mL), C(max) (.251 vs. .243 ng/mL) and T(max) (.75 vs.1.08 h). Objective opioid withdrawal was not observed. The AUC(0-12 h) and C(max) of raltegravir did not significantly differ from historical controls (5543 vs. 4428 h*ng/mL and 1070 vs. 1266 ng/mL), respectively.
  
  
  CONCLUSIONS
  The addition of raltegravir to stabilized patients receiving buprenorphine/naloxone does not significantly affect buprenorphine/naloxone or raltegravir pharmacokinetic or pharmacodynamic parameters.
authors: Yale University AIDS Program, New Haven, CT 06510, USA. Robert.bruce@yale.edu
authors: R
authors: R
authors: Douglas Bruce
authors: David E
authors: DE
authors: Moody
authors: Diane
authors: D
authors: Chodkowski
authors: Laurie
authors: L
authors: Andrews
authors: Wenfang B
authors: WB
authors: Fang
authors: Jerdravee
authors: J
authors: Morrison
authors: Theresa L
authors: TL
authors: Parsons
authors: Gerald H
authors: GH
authors: Friedland
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors; D018023:HIV Seronegativity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D058850:Opiate Substitution Treatment / Q000009:adverse effects; D011760:Pyrrolidinones / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D009292:Narcotic Antagonists; D011760:Pyrrolidinones; D009270:Naloxone; D002047:Buprenorphine; D000068898:Raltegravir Potassium; D014453:Glucuronosyltransferase