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Steady-State Pharmacokinetics of Etravirine and Lopinavir/Ritonavir Melt Extrusion Formulation, Alone and in Combination, in Healthy HIV-Negative Volunteers

Authors


  • Data previously presented in part at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco, California, USA, September 12-15, 2009, Poster A1-1298, and the 12th European AIDS Conference, Cologne, Germany, November 11-14, 2009, Poster PE4.3/1.

Corresponding Author:

Richard M. W. Hoetelmans, PhD, Tibotec BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium Email: RHOETELM@its.jnj.com

Abstract

Background

A previous study investigating coadministration of etravirine, a nonnucleoside reverse transcriptase inhibitor, and lopinavir/ritonavir soft-gel formulation resulted in nonclinically relevant changes in etravirine and lopinavir exposure. The current study evaluated the pharmacokinetic interaction between etravirine and the lopinavir/ritonavir melt extrusion formulation.

Method

Sixteen human immunodeficiency virus (HIV)-negative volunteers were randomized to either treatment sequence A/B or B/A, with 14 days— washout between treatments (treatment A: etravirine 200 mg bid for 8 days; treatment B: lopinavir/ritonavir 400/100 mg bid for 16 days with etravirine 200 mg bid on days 9-16). Steady-state pharmacokinetics were assessed for all antiretrovirals alone and coadministered; pharmacokinetic parameters were obtained by noncompartmental analysis. Safety and tolerability were assessed.

Results

Coadministration of etravirine and lopinavir/ritonavir resulted in a 35% decrease in etravirine exposure. Smaller decreases (<13%) were observed in lopinavir and ritonavir exposure. Six volunteers reported headache; 1 grade 3 triglyceride increase was reported.

Conclusion

Lopinavir/ritonavir induced etravirine metabolism to a similar extent as most other boosted HIV protease inhibitors. The short-term coadministration of etravirine and lopinavir/ritonavir was well tolerated and did not lead to increased incidences of adverse events.

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