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Antimicrobial Agents and Chemotherapy, April 2007, p. 1431-1439, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00854-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Saquinavir, Atazanavir, and Ritonavir in a Twice-Daily Boosted Double-Protease Inhibitor Regimen{triangledown}

Nils von Hentig,1* Axel Müller,2 Carsten Rottmann,2 Timo Wolf,2 Thomas Lutz,3 Stephan Klauke,4 Michael Kurowski,5 Bruno Oertel,1 Brenda Dauer,2 Sebastian Harder,1 and Schlomo Staszewski2

Pharmazentrum Frankfurt,1 HIV Treatment and Clinical Research Unit at the J. W. Goethe University Hospital, Frankfurt,2 private practice, Grueneburgweg,3 ifs Stresemannallee, Frankfurt,4 Therapia GmbH at the Auguste Victoria Hospital, Berlin, Germany5

Received 13 July 2006/ Returned for modification 31 October 2006/ Accepted 21 December 2006

The objective of this study was to evaluate the pharmacokinetics of atazanavir (ATV), saquinavir (SQV), and ritonavir (RTV) in a boosted double-protease inhibitor (PI) therapy regimen without reverse transcriptase inhibitors (RTIs). The study design was as follows. Patients with limited RTI options received a PI combination of 300/100 mg ATV/RTV once daily and 1,000 mg SQV twice daily (group 1; n = 49) without RTI comedication. The results were compared to the plasma concentrations of PIs of patients taking either 300 mg ATV/100 mg RTV once daily plus RTIs (group 2; n = 72) or patients taking 1,000 mg SQV/100 mg RTV plus RTIs (group 3; n = 90). The study methods were as follows. Patients were given a 12/24-h pharmacokinetic assessment at steady state. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. The minimum and maximum concentrations (Cmin and Cmax), area under the concentration-time curve under steady-state conditions (AUCss), elimination half-life, time of maximum concentration and lag time were subject to statistical analysis. The results show that patients treated with ATV/SQV/RTV exhibited significantly high SQV concentrations and moderate enhancement of the AUCss of ATV in comparison to those of patients of the control groups: for SQV in groups 1 and 3, the geometric mean (GM) of the AUCss was 22,794 versus 15,759 ng·h/ml (GM ratio [GMR] = 1.45; P < 0.05), the GM of the Cmax was 3,257 versus 2,331 ng/ml (GMR = 1.40; P < 0.05), and the GM of the Cmin was 438 versus 437 ng/ml (GMR = 1.00); for ATV in groups 1 and 2, the GM of the AUCss was 39,154 versus 33,626 ng·h/ml (GMR = 1.16), the GM of the Cmax was 3,488 versus 2,924 ng/ml (GMR = 1.20), and the GM of the Cmin was 515 versus 428 ng/ml (GMR = 1.21). RTV levels were comparable for all groups. A subgroup analysis detected only marginal differences in ATV plasma exposure if combined with tenofovir-disoproxilfumarate and without it. We conclude that our pharmacokinetic results support the use of a boosted double-PI regimen of ATV/SQV/RTV as a treatment option for patients who need antiretroviral therapy without RTIs.

* Corresponding author. Mailing address: Pharmazentrum, J. W. Goethe University Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Phone: 49-69-63016956. Fax: 49-69-63017636. E-mail: Hentig{at}em.uni-frankfurt.de

{triangledown} Published ahead of print on 12 February 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1431-1439, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00854-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • von Hentig, N., Kaykhin, P., Stephan, C., Babacan, E., Sturmer, M., Staszewski, S., Lotsch, J. (2008). Decrease of Atazanavir and Lopinavir Plasma Concentrations in a Boosted Double Human Immunodeficiency Virus Protease Inhibitor Salvage Regimen. Antimicrob. Agents Chemother. 52: 2273-2275 [Abstract] [Full Text]  


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