CLINICAL STUDY: Effect of saquinavir/ritonavir (1000/100 mg bid) on the pharmacokinetics of methadone in opiate‐dependent HIV‐negative patients on stable methadone maintenance therapy

Abstract

This study was performed to determine the effect of two protease inhibitors, saquinavir (SQV, oral 1000 mg bid) boosted by ritonavir (RTV, oral 100 mg bid), on pharmacokinetics (PK) of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapy. This was a two-center, open-label, one-sequence cross-over, multiple-dose study in 13 HIV-negative patients who were on stable methadone therapy (oral, 60-120 mg qd). All patients continued methadone treatment on days 2-15. All patients received SQV/RTV in combination with methadone from days 2-15. PK of methadone was assessed on day 1 (alone) and on day 15 when methadone treatment was combined with SQV/RTV at steady state. Twelve patients completed the study. Median age, body weight and height were 50 years (range: 24-54 years), 80 kg (range: 57-97 kg) and 174 cm (range: 163-189 cm), respectively. All patients were Caucasian, and 11 were smokers. Median methadone dose was 85 mg qd. Geometric mean area under curve of the plasma concentration-time curve over 24 hour dosing interval (AUC(0-24 hour)) ratio of methadone with and without SQV/RTV was 0.81% (90% confidence interval: 71-91%). There was no significant plasma protein-binding displacement of methadone by SQV/RTV. The combination of SQV/RTV and methadone was well tolerated. There were no clinically significant adverse events or significant changes in laboratory parameters, electrocardiograms or vital signs. The 19% decrease in R-methadone AUC(0-24 hour) in the presence of SQV/RTV was not clinically relevant. There appears to be no need for methadone dose adjustment when methadone (60-120 mg qd) and SQV/RTV (1000/100 mg bid) are coadministered.