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01-09-2009 | Review Article

Clinical Pharmacokinetics and Pharmacodynamics of Etravirine

Authors: Dr Monika Schöller-Gyüre, Thomas N. Kakuda, Araz Raoof, Goedele De Smedt, Richard M. W. Hoetelmans

Published in: Clinical Pharmacokinetics | Issue 9/2009

Abstract

Etravirine is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) developed for the treatment of HIV-1 infection. It has a high genetic barrier to the emergence of viral resistance, and maintains its antiviral activity in the presence of common NNRTI mutations. The pharmacokinetics of etravirine in HIV-infected patients at the recommended dosage of 200 mg twice daily demonstrates moderate intersubject variability and no time dependency. Due to substantially lower exposures when taken on an empty stomach, etravirine should be administered following a meal. The drug is highly protein bound (99.9%) to albumin and α₁-acid glycoprotein and shows a relatively long elimination half-life of 30–40 hours. Etravirine is metabolized by cytochrome P450 (CYP) 3A, 2C9 and 2C19; the metabolites are subsequently glucuronidated by uridine diphosphate glucuronosyltransferase. Renal elimination of etravirine is negligible. Etravirine has the potential for interactions by inducing CYP3A and inhibiting CYP2C9 and 2C19; it is a mild inhibitor of P-glycoprotein but not a substrate. The drug interaction profile of etravirine has been well characterized and is manageable. No dosage adjustments are needed in patients with renal impairment or mild to moderate hepatic impairment. Race, sex, bodyweight and age do not affect the pharmacokinetics of etravirine. In the two phase III trials DUET-1 and DUET-2, no relationship was demonstrated between the pharmacokinetics of etravirine and the primary efficacy endpoint of viral load below 50 copies/mL or the safety profile of etravirine.

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Title: Clinical Pharmacokinetics and Pharmacodynamics of Etravirine
Authors: Dr Monika Schöller-Gyüre
Thomas N. Kakuda
Araz Raoof
Goedele De Smedt
Richard M. W. Hoetelmans
Publication date: 01-09-2009
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 9/2009
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.2165/10895940-000000000-00000

Keynote webinar | Spotlight on medication adherence

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Clinical Pharmacokinetics and Pharmacodynamics of Etravirine

Abstract

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