Pharmacokinetic interactions between buprenorphine/naloxone and raltegravir in subjects receiving chronic buprenorphine/naloxone treatment.

Background: Interactions between human immuno-deficiency virus (HIV) and opioid-dependence therapies can occur.

Objectives: 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.

Conclusion: The addition of raltegravir to stabilized patients receiving buprenorphine/naloxone does not significantly affect buprenorphine/naloxone or raltegravir pharmacokinetic or pharmacodynamic parameters.