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Tenofovir comedication does not impair the steady-state pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected adults

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Our objective was to evaluate the steady-state pharmacokinetics of ritonavir-boosted atazanavir when coadministered with tenofovir in HIV-1-infected adult patients.

Design

Forty adult HIV-1-infected patients received either atazanavir/ritonavir 300/100 mg once daily and nucleoside reverse transcriptase inhibitors with (n = 20) or without (n = 20) tenofovir-disoproxil fumarate (tenofovir-DF) 300 mg once daily. Twenty-four-hour pharmacokinetics were assessed after at least 2 weeks of therapy according to a standardised therapeutic drug monitoring protocol.

Methods

Atazanavir/ritonavir plasma concentrations were measured by liquid chromatography tandem mass spectrometry, and the geometric means of minimum and maximum concentrations (Cmin, Cmax), the area under the time-concentration curve (AUC), half-life (t1/2) and total clearance (CLtot) were subject to a matched pairs-analysis. Patients’ pairs were matched for gender, ethnicity, weight and Center for Disease Control and Prevention (CDC) status.

Results

The respective geometric means (90% CI) for atazanavir Cmin, Cmax and AUC with tenfovir vs. without tenofovir were 405 (314–523) vs. 417 (304–572) ng/ml, 3,022 (2,493–3,664) vs. 2,817 (2,341–3,390) ng/ml and 34,822 (29,315–41,363) vs. 32,101 (26,206–39,321) ng × h/ml showing no significant differences between the groups. Atazanavir plasma concentrations measured at week 5 of therapy or later were lower than in the first 4 weeks (T-test for Cmax, p = .080; AUC, p = .050 and CLtot, p = .051).

Conclusions

The coadministration of tenofovir-DF did not impair the plasma concentrations of ritonavir-boosted atazanavir in a pharmacokinetic analysis of patient pairs matched for gender, ethnicity, weight and CDC status.

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Acknowledgement

The authors have no financial conflict of interest and no financial support was received for this study. Preliminary data from this study were presented in part at the ASCPT Annual Meeting 2005, Orlando, FL, USA (Abstract PI-40).

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Authors and Affiliations

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

    Nils von Hentig & Sebastian Harder

  2. Medical HIV-Treatment and Research Unit, JohannWolfgang Goethe University Hospital Frankfurt, Frankfurt, Germany

    Brenda Dauer, Annette Haberl & Schlomo Staszewski

  3. IFS Stresemannallee 3, Frankfurt, Germany

    Stefan Klauke

  4. Infektiologicum Frankfurt, Frankfurt, Germany

    Thomas Lutz

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  1. Nils von Hentig
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  2. Brenda Dauer
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Correspondence to Nils von Hentig.

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von Hentig, N., Dauer, B., Haberl, A. et al. Tenofovir comedication does not impair the steady-state pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected adults. Eur J Clin Pharmacol 63, 935–940 (2007). https://doi.org/10.1007/s00228-007-0344-y

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  • DOI: https://doi.org/10.1007/s00228-007-0344-y

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