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

Autar, R. S.; Ananworanich, J.; Apateerapong, W.; Sankote, J.; Hill, A.; Hirschel, Bernard; Cooper, David; Lange, Joep; Phanuphak, P.; Ruxrungtham, K.; Burger, Danielle

doi:10.1093/jac/dkh415

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Title		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
Authors		Autar, R. S. Ananworanich, J. Apateerapong, W. Sankote, J. Hill, A. Hirschel, Bernard Cooper, David Lange, Joep Phanuphak, P. Ruxrungtham, K. Burger, Danielle show all authors [1 - 11]
Published in		Journal of Antimicrobial Chemotherapy. 2004, vol. 54, no. 4, p. 785-790
Abstract		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		Adult — Antiretroviral Therapy, Highly Active — Capsules — Drug Administration Schedule — Female — Gels — HIV Infections/ drug therapy/metabolism — HIV-1/ drug effects — Humans — Male — Metabolic Clearance Rate — Ritonavir/administration & dosage/ pharmacokinetics/therapeutic use — Saquinavir/administration & dosage/ pharmacokinetics/therapeutic use
Identifiers		DOI: 10.1093/jac/dkh415 PMID: 15329366
Full text		Article - Limited access to UNIGE Other version: http://jac.oxfordjournals.org/cgi/reprint/54/4/785.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		AUTAR, R. S. et al. 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. In: Journal of Antimicrobial Chemotherapy, 2004, vol. 54, n° 4, p. 785-790. doi: 10.1093/jac/dkh415 https://archive-ouverte.unige.ch/unige:7089