Pharmacokinetic study of saquinavir hard gel caps/ritonavir in HIV-1-infected patients: 1600/100 mg once-daily compared with 2000/100 mg once-daily and 1000/100 mg twice-daily

Objectives: A pharmacokinetic comparison of three dosing regimens of saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. Methods: Twenty patients on saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC(0-24) or AUC(0-12)), maximum and minimum concentration (C-max and C-min) and elimination half-life were calculated using a non-compartmental model. Results: Compared with saquinavir/ritonavir 1600/100 mg once-daily dosing, the saquinavir AUC and C-min improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low C-min in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in saquinavir C-max (52%) compared with saquinavir/ritonavir 1600/100 mg once-daily. Conclusions: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher saquinavir plasma levels compared with saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.