Clinical pharmacokinetics and pharmacodynamics of etravirine.
Article Details
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Scholler-Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM
Clinical pharmacokinetics and pharmacodynamics of etravirine.
Clin Pharmacokinet. 2009;48(9):561-74. doi: 10.2165/10895940-000000000-00000.
- PubMed ID
- 19725591 [ View in PubMed]
- 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 alpha(1)-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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Etravirine Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails Etravirine Cytochrome P450 2C9 Protein Humans UnknownSubstrateInhibitorDetails Etravirine Cytochrome P450 3A4 Protein Humans UnknownSubstrateInducerDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Etravirine Multidrug resistance protein 3 Protein Humans UnknownInhibitorDetails Etravirine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareEtravirinePhenytoin The serum concentration of Etravirine can be decreased when it is combined with Phenytoin. EtravirineFosphenytoin The serum concentration of Etravirine can be decreased when it is combined with Fosphenytoin. EtravirineRitonavir The serum concentration of Etravirine can be decreased when it is combined with Ritonavir.