The Effects of Once-Daily Saquinavir/Minidose Ritonavir on the Pharmacokinetics of Methadone

Twelve methadone‐maintained HIV‐negative subjects were given saquinavir/ritonavir (SQV/rtv) 1600 mg/100 mg once daily for 14 days. Pharmacokinetic evaluations of total and unbound methadone enantiomers (R and S) were conducted before and after SQV/rtv. SQV/rtv was well tolerated, with no ACTG Grade 3–4 adverse events, no evidence of sedation, and no changes in methadone dose. For R‐methadone (active isomer), Cmax, AUC0–24 h, and Cmin were unchanged, but percent unbound 4 hours after dosing was reduced by 12%. For S‐methadone, no differences in pharmacokinetic parameters of total drug were seen, but unbound concentrations were reduced by 15% and 21% at 4 and 24 hours after dosing, respectively. SQV trough concentrations exceeded the anticipated EC50 (50 ng/mL) in 10/12 subjects, persisting for at least 6 hours after the final dose in 4/6 subjects. Once‐daily SQV/rtv in methadone‐maintained subjects is safe and not associated with any clinically significant interaction with methadone during 14 days of concomitant administration.