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), C_max, AUC _0-24h, and C_min 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.