The Effects of Once-daily Saquinavir/Low-dose 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(0-24 h), 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 EC(50) (50 ng/mL) in 10/12 subjects, persisting for at least 6 hours after the final dose in 4/6 subjects.

In conclusion, the authors note, “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.”

03/10/04

Reference
M J Shelton and others.  The effects of once-daily saquinavir/minidose ritonavir on the pharmacokinetics of methadone. Journal of Clinical Pharmacology 44(3): 293-304. March 2004.