title: Pharmacokinetics of saquinavir, atazanavir, and ritonavir in a twice-daily boosted double-protease inhibitor regimen.
abstract: 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.
authors.affiliation: Pharmazentrum Frankfurt and HIV Treatment and Clinical Research Unit at the J.W. Goethe University Hospital, Frankfurt, Germany. Hentig@em.uni-frankfurt.de
authors.forename: Nils
authors.initials: N
authors.lastname: von Hentig
authors.forename: Axel
authors.initials: A
authors.lastname: Müller
authors.forename: Carsten
authors.initials: C
authors.lastname: Rottmann
authors.forename: Timo
authors.initials: T
authors.lastname: Wolf
authors.forename: Thomas
authors.initials: T
authors.lastname: Lutz
authors.forename: Stephan
authors.initials: S
authors.lastname: Klauke
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
authors.forename: Bruno
authors.initials: B
authors.lastname: Oertel
authors.forename: Brenda
authors.initials: B
authors.lastname: Dauer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012449:Safety; D019258:Saquinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019258:Saquinavir; D019438:Ritonavir