Taking the Convenience of Once-daily Dosing into Consideration, Saquinavir/Ritonavir 2000/100 mg Once-daily May Be the Peferred Dosing Regimen

This study involved 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.

Preliminary results of the study appeared as a poster at the European AIDS Cconference (EACS) in Warsaw last year (October 25-29, 2003).

Twenty patients on saquinavir hard gel caps (Invirase)/ritonavir (Norvir) 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 (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) 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 Cmin 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 Cmin 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 Cmax (52%) compared with saquinavir/ritonavir 1600/100 mg once-daily.

Conclusions

The authors conclude, “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.”

The HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, The Thai Red Cross AIDS Research Center, Bangkok, Thailand; International Antiviral Therapy Evaluation Center, Amsterdam, The Netherlands.

09/08/04

Reference
R S Autar and others. 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. Journal of  Antimicrobial Chemotherapy. August 25, 2004 [Epub ahead of print].