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JAC Advance Access originally published online on August 25, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(4):785-790; doi:10.1093/jac/dkh415
JAC vol.54 no.4 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved

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

R. S. Autar1,2,*, J. Ananworanich1, W. Apateerapong1, J. Sankote1, A. Hill3, B. Hirschel4, D. Cooper1,5, J. Lange1,2,6, P. Phanuphak1,7, K. Ruxrungtham1,7 and D. Burger8

1 The HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, The Thai Red Cross AIDS Research Center, Bangkok; 7 Department of Medicine, Faculty of Medicine, Chulalongkorn University, Thailand; 2 International Antiviral Therapy Evaluation Center, Amsterdam; 6 Academic Medical Center, University of Amsterdam; 8 University Medical Centre, Nijmegen, The Netherlands; 3 Roche, Welwyn Garden City, UK; 4 Geneva University Hospital, Geneva, Switzerland; 5 National Center in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia

* Corresponding author. Present address: 104 Radjumri Road, Pathumwan 10330, Bangkok, Thailand. Tel: +66-2255-7334; Fax: +66-2252-5779; Email: saskia{at}hivnat.com

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 (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: 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.

Keywords: protease inhibitors , HIV , Thailand , pharmacokinetics


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