Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir

J Acquir Immune Defic Syndr. 2010 Aug;54(5):511-4. doi: 10.1097/qai.0b013e3181d3cad3.

Abstract

Background: This study was conducted to examine the pharmacokinetic interactions between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV-seronegative subjects chronically maintained on BUP/NLX.

Methods: This study was an open labeled pharmacokinetic study in twelve HIV-seronegative subjects stabilized on at least 3 weeks of BUP/NLX therapy. Subjects sequentially underwent baseline and steady-state pharmacokinetic evaluation of once-daily LPV/r (800/200 mg).

Results: Compared to baseline values, BUP AUC0-24h (46.8 vs. 46.2 ng*hr/mL) and Cmax (6.54 vs. 5.88 ng/mL) did not differ significantly after achieving steady-state LPV/r. Similar analyses of norBUP, the primary metabolite of BUP, demonstrated no significant difference in norBUP AUC0-24 hours (73.7 vs. 52.7 ng x h/mL); however, Cmax (5.29 vs. 3.11 ng/mL) levels were statistically different (P < 0.05) after LPV/r administration. Naloxone concentrations were similarly unchanged for AUC0-24 hours (0.421 vs. 0.374 ng x hr/mL) and Cmax (0.186 vs. 0.186 ng/mL). Using standardized measures, no objective opioid withdrawal was observed. The AUC0-24 hours and Cmin of LPV in this study did not significantly differ from historical controls (159.6 vs. 171.3 microg x hr/mL) and (2.3 vs. 1.3 microg/mL).

Conclusions: The addition of LPV/r to stabilized patients receiving BUP/NLX did not affect buprenorphine pharmacokinetics but did increase the clearance of norbuprenorphine. Pharmacodynamic responses indicate that the altered norbuprenorphine clearance did not lead to opioid withdrawal. Buprenorphine/naloxone and LPV/r can be safely coadministered without need for dosage modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / pharmacokinetics*
  • Analgesics, Opioid / therapeutic use
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Buprenorphine / pharmacokinetics*
  • Buprenorphine / therapeutic use
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lopinavir
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Naloxone / pharmacokinetics*
  • Naloxone / therapeutic use
  • Pyrimidinones / pharmacokinetics*
  • Pyrimidinones / therapeutic use
  • Ritonavir / pharmacokinetics*
  • Ritonavir / therapeutic use

Substances

  • Analgesics, Opioid
  • Anti-HIV Agents
  • Pyrimidinones
  • Lopinavir
  • Naloxone
  • Buprenorphine
  • Ritonavir