Steady-state pharmacokinetics of a double-boosting regimen of saquinavir soft gel plus lopinavir plus minidose ritonavir in human immunodeficiency virus-infected adults

Esteban Ribera, Rosa M. Lopez, Marjorie Diaz, Leonor Pou, Lidia Ruiz, Vicenç Falcó, Manuel Crespo, Carlos Azuaje, Isabel Ruiz, Imma Ocaña, Bonaventura Clotet, Albert Pahissa

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Abstract

Management of treatment-experienced human immunodeficiency virus patients has become complex, and therapy may need to include two protease inhibitors at therapeutic doses. The objective of this study was to characterize the pharmacokinetics in serum of saquinavir (1,000 mg twice daily [b.i.d.]), lopinavir (400 mg b.i.d.), and ritonavir (100 mg b.i.d.) in a multidrug rescue therapy study and to investigate whether steady-state pharmacokinetics of lopinavir-ritonavir are affected by coadministration of saquinavir. Forty patients were included (25 given ritonavir, lopinavir, and saquinavir and 15 given ritonavir and lopinavir). The median pharmacokinetic parameters of lopinavir were as follows: area under the concentration-time curve from 0 to 12 h (AUC0-12) 85.1 μg/ml · h; and maximum concentration of drug in serum (Cmax), 10.0 μg/ml; trough concentration of drug in serum (Ctrough), 73 μg/ml; and minimum concentration of drug in serum (Cmin), 5.5 μg/ml. Lopinavir concentrations were similar in patients with and without saquinavir. The median pharmacokinetic parameters for saquinavir were as follows: AUC0-12, 22.9 μg/ml · h; C max, 2.9 μg/ml; Ctrough, 1.6 μg/ml; and C min, 1.4 μg/ml. There was a strong linear correlation between lopinavir and ritonavir and between saquinavir and ritonavir concentrations in plasma. The correlation between lopinavir and saquinavir levels was weaker. We found higher saqainavir concentrations in women than in men, with no difference in lopinavir levels. Only patients with very high body weight presented lopinavir and saquinavir concentrations lower than the overall group. Ritonavir has a double-boosting function for both lopinavir and saquinavir, and in terms of pharmacokinetics, the drug doses selected seemed appropriate for combining these agents in a dual protease inhibitor-based antiretroviral regimen for patients with several prior virologic failures.
Original languageEnglish
Pages (from-to)4256-4262
JournalAntimicrobial Agents and Chemotherapy
Volume48
Issue number11
DOIs
Publication statusPublished - 1 Nov 2004

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