Buprenorphine and naloxone pharmacokinetics before and after 10 days of once daily lopinavir/ritonavir (800/200 mg) were determined in 12 HIV- subjects stable on buprenorphine/naloxone therapy. Lopinavir/ritonavir had no significant effect on buprenorphine AUC (46.9 vs 46.2 ng.h/ml) and Cmax (6.54 vs 5.88 ng/ml). Similarly, there was no significant effect on the AUC of norbuprenorphine (73.7 vs 52.7 ng.h/ml); however, apparent oral clearance of the metabolite significantly increased (4.87 vs 6.79 L/min; P < 0.05) and Cmax significantly decreased (5.29 vs 3.11 ng/ml; P < 0.05) in the presence of lopinavir/ritonavir. There was no effect on naloxone AUC (0.421 vs 0.374 ng.h/ml) or Cmax (0.186 vs 0.186 ng/ml). When compared to historical data, there was no effect of buprenorphine/naloxone on lopinavir AUC or Cmin. The altered norbuprenorphine clearance did not lead to objective opioid withdrawal and therefore buprenorphine/naloxone can be administered with lopinavir/ritonavir without dose modification.
Pharmacokinetic interactions between buprenorphine/naloxone and once daily lopinavir/ritonavir. Bruce RD, Altice FL, Moody DE, et al. J Acquir Immune Defic Syndr, 2010, 54(5): 511-514. The effect of lopinavir (400/100 mg twice daily) on the pharmacokinetics of buprenorphine (16 mg daily in combination with naloxone) was examined in 10 HIV-subjects. There were no significant changes in buprenorphine AUC, Cmax or Cmin when given with lopinavir/ritonavir, and coadministration was not associated with opiate withdrawal symptoms. When compared with data from a control group receiving lopinavir/ritonavir alone (n=15), buprenorphine increased lopinavir AUC by ~15%, with no significant change in Cmax or Cmin.
Interactions between buprenorphine and antiretrovirals. II. The protease inhibitors nelfinavir, lopinavir/ritonavir, and ritonavir. McCance-Katz EF, Moody DE, Smith PF, et al. Clin Infect Dis, 2006, 43 (Suppl 4): S235-246.