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

  • Nils von Hentig
  • Brenda Dauer
  • Annette Haberl
  • Stefan Klauke
  • Thomas Lutz
  • Schlomo Staszewski
  • Sebastian Harder
Pharmacokinetics and Disposition

DOI: 10.1007/s00228-007-0344-y

Cite this article as:
von Hentig, N., Dauer, B., Haberl, A. et al. Eur J Clin Pharmacol (2007) 63: 935. doi:10.1007/s00228-007-0344-y

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.

Keywords

HAART Drug-drug interaction TDM Atazanavir Tenofovir-DF 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Nils von Hentig
    • 1
  • Brenda Dauer
    • 2
  • Annette Haberl
    • 2
  • Stefan Klauke
    • 3
  • Thomas Lutz
    • 4
  • Schlomo Staszewski
    • 2
  • Sebastian Harder
    • 1
  1. 1.Pharmazentrum Frankfurt/ZAFES, Institute of Clinical PharmacologyJohann Wolfgang Goethe UniversityFrankfurt am MainGermany
  2. 2.Medical HIV-Treatment and Research UnitJohannWolfgang Goethe University Hospital FrankfurtFrankfurtGermany
  3. 3.FrankfurtGermany
  4. 4.Infektiologicum FrankfurtFrankfurtGermany

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