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Antimicrobial Agents and Chemotherapy, August 2009, p. 3524-3527, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00025-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cytochrome P450 3A Inhibition by Atazanavir and Ritonavir, but Not Demography or Drug Formulation, Influences Saquinavir Population Pharmacokinetics in Human Immunodeficiency Virus Type 1-Infected Adults{triangledown}

Nils von Hentig and Jörn Lötsch*

pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany

Received 7 January 2009/ Returned for modification 8 May 2009/ Accepted 3 June 2009

Inadequate concentrations of the human immunodeficiency virus (HIV) protease inhibitor saquinavir jeopardize individual therapy success or produce side effects despite treatment according to the current guidelines. We performed a population pharmacokinetic analysis with NONMEM and determined that the steady-state pharmacokinetics of saquinavir in 136 HIV type 1-infected adults was modulated by a decrease in saquinavir CL following coadministration of the cytochrome P450 3A inhibitors ritonavir and atazanavir. In contrast, age, sex, weight, pregnancy, and the pharmaceutical formulation exerted only minor, nonsignificant effects.

* Corresponding author. Mailing address: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. Phone: 49-69-6301-4589. Fax: 49-69-6301-7636. E-mail: j.loetsch{at}em.uni-frankfurt.de

{triangledown} Published ahead of print on 15 June 2009.

Antimicrobial Agents and Chemotherapy, August 2009, p. 3524-3527, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00025-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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