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Antimicrobial Agents and Chemotherapy, November 2004, p. 4256-4262, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4256-4262.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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,1* Rosa M. Lopez,2 Marjorie Diaz,1 Leonor Pou,3 Lidia Ruiz,4 Vicenç Falcó,1 Manuel Crespo,1 Carlos Azuaje,1 Isabel Ruiz,1 Imma Ocaña,1 Bonaventura Clotet,4 and Albert Pahissa1

Infectious Disease Service,1 Pharmacy Service,2 Clinical Biochemistry Service, Hospital Universitari Vall d’Hebron, Autonomous University of Barcelona,3 Fundació Irsi-Caixa-Hospital Germans Trias i Pujol, Barcelona, Spain4

Received 7 January 2004/ Returned for modification 20 February 2004/ Accepted 29 June 2004

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; maximum concentration of drug in serum (Cmax), 10.0 µg/ml; trough concentration of drug in serum (Ctrough), 7.3 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; Cmax, 2.9 µg/ml; Ctrough, 1.6 µg/ml; and Cmin, 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 saquinavir 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.

* Corresponding author. Mailing address: Servicio de Enfermedades Infecciosas, Hospital Universitari Vall d’Hebron, Paseo Vall Hebron 119-129, 08035 Barcelona, Spain. Phone: 934 894497. Fax: 934 282762. E-mail: eribera{at}vhebron.net.

Antimicrobial Agents and Chemotherapy, November 2004, p. 4256-4262, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4256-4262.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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