JAC Advance Access originally published online on May 13, 2008
Journal of Antimicrobial Chemotherapy 2008 62(3):579-582; doi:10.1093/jac/dkn204
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Original research |
The steady-state pharmacokinetics of atazanavir/ritonavir in HIV-1-infected adult outpatients is not affected by gender-related co-factors
1 Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Frankfurt, Germany 2 HIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University, Frankfurt, Germany 3 Infektiologikum Frankfurt, Frankfurt, Germany
Received 17 December 2007; returned 26 February 2008; revised 11 April 2008; accepted 15 April 2008
* Corresponding author. Tel: +49-69-63016956; Fax: +49-69-63017636; E-mail: hentig{at}em.uni-frankfurt.de
Objectives: Pharmacokinetic differences, contributing to drug-related side effects, between men and women have been reported for HIV protease inhibitors. As only limited and inconclusive data on ritonavir-boosted atazanavir are available, we evaluated the respective steady-state pharmacokinetics in 48 male and 26 female HIV-1-infected adults receiving atazanavir/ritonavir 300/100 mg once-daily as part of their antiretroviral therapy.
Methods: Pharmacokinetic profiles (24 h) of atazanavir/ritonavir were assessed and measured by HPLC/tandem mass spectrometry. Geometric mean (GM; ANOVA) of minimum and maximum plasma drug concentrations (Cmin and Cmax), area under the concentration–time curve (AUC) and total clearance (CLtotal) were compared between the sexes and correlated to demographic (age, gender and ethnicity), physiological (weight and body mass index) and clinical (CD4+ cell count, HIV-RNA, co-medication and hepatitis serology) co-factors.
Results: The GM of the atazanavir AUC, Cmax and Cmin of men versus women were 32 643 versus 36 232 ng·h/mL [GM ratio (GMR) = 1.11, P = 0.435], 2802 versus 3211 ng/mL (GMR = 1.15, P = 0.305) and 398 versus 470 ng/mL (GMR = 1.18, P = 0.406), respectively. Although weight (80.6 versus 63.9 kg, P = 0.001) and body weight-adjusted atazanavir dose (3.84 versus 4.60 mg/kg, P = 0.013) were different between the sexes, no significant correlation to atazanavir pharmacokinetics was observed. A linear regression analysis detected significant correlations of atazanavir Cmin with ritonavir AUC (P < 0.001) and the co-administration of methadone oral solution (P = 0.032), and inverse correlations with the time since the first HIV infection diagnosis (P = 0.003) and the number of previous antiretroviral treatments (P = 0.022).
Conclusions: Atazanavir/ritonavir steady-state pharmacokinetics was comparable in men and women, despite gender-related significant differences in atazanavir dose/body weight. The administration of atazanavir/ritonavir is pharmacokinetically safe; 95% of all trough samples were above the recommended plasma concentration of 150 ng/mL.
Keywords: HIV protease inhibitors , antiviral , antiretroviral therapy
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  L. Dickinson, M. Boffito, D. Back, L. Waters, L. Else, G. Davies, S. Khoo, A. Pozniak, and L. Aarons Population pharmacokinetics of ritonavir-boosted atazanavir in HIV-infected patients and healthy volunteers J. Antimicrob. Chemother., June 1, 2009; 63(6): 1233 - 1243. [Abstract] [Full Text] [PDF]
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