Tenofovir comedication does not impair the steady-state pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected adults
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- von Hentig, N., Dauer, B., Haberl, A. et al. Eur J Clin Pharmacol (2007) 63: 935. doi:10.1007/s00228-007-0344-y
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Our objective was to evaluate the steady-state pharmacokinetics of ritonavir-boosted atazanavir when coadministered with tenofovir in HIV-1-infected adult patients.
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.
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.
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).
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.