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Original article

Pharmacokinetics of once-daily etravirine without and with once-daily darunavir/ritonavir in antiretroviral-naive HIV type-1-infected adults

Edwin DeJesus, Jacob P Lalezari, Olayemi O Osiyemi, Peter J Ruane, Robert Ryan, Thomas N Kakuda, James Witek

Corresponding author name: Edwin DeJesus
Corresponding author e-mail: edejesus@oicorlando.com

Citation: Antiviral Therapy 2010; 15:711-720
doi: 10.3851/IMP1562

Date accepted: 11 January 2010
Date published online: 04 June 2010

Abstract

Background: A pharmacokinetic trial was conducted to evaluate the potential for once-daily etravirine in antiretroviral regimens without and with darunavir/ritonavir.

Methods: During this multicentre, open-label, Phase IIa trial, treatment-naive patients aged18 years with HIV type-1 (HIV-1) received etravirine 400 mg once daily with tenofovir disoproxil fumarate/emtricitabine 300/200 mg once daily from days 1–14; on days 15–28, darunavir/ritonavir 800/100 mg once daily was added. On day 29, etravirine was discontinued and patients continued with the other medications to day 42. Serial blood sampling for etravirine pharmacokinetics was performed over 24 h on day 14 and 28; patients fasted for10 h prior to these visits.

Results: Of 23 enrolled patients (male 87%, Caucasian 39%), pharmacokinetic profiles for etravirine were available for 21 and 20 patients on day 14 and 28, respectively. The plasma concentration–time profile and pharmacokinetics for etravirine were unchanged with or without darunavir/ritonavir. The mean maximum plasma concentration (Cmax) was reached 4 h after administration and was 790 and 801 ng/ml on day 14 and 28, respectively; mean area under the plasma concentration–time curve (AUC) from before administration to 24 h after administration was 10,410 ng•h/ml on day 14 and 10,720 ng•h/ml on day 28. In a post-hoc analysis, etravirine Cmax was higher, minimum plasma concentration was lower and AUC was similar when compared with etravirine 200 mg twice daily.

Conclusions: Addition of darunavir/ritonavir to etravirine, all dosed once daily, did not have a clinically significant effect on the pharmacokinetics of etravirine. Findings support further investigation of etravirine 400 mg once daily in HIV-1-infected patients. (Trial registration number NCT00534352.)

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