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Pharmacokinetic Interactions Between Rifampicin and Efavirenz in HIV-TB Coinfections

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The increased percentage of patients with HIV-TB coinfection leads to inevitable interactions between rifapincin and efavirenz Efavirenz is a potent non-nucoside reverse transcripate inhibitor (NNRT) for the treatment of HIV infection. The use of this drug combination with rifampicin causes problem in determination of the optiml dosage of efavirenz when adminstered concomitanly with refapicin.Efavirenz is metabolized by the enzyme cytochrome P-450 (CYP), i.e. the CYP2B6 and CYP3A4 isozymes, of which rifampicin is an inducer. The induction of cytochrome P-450 by rifampicin is mediated by pregnane X (PXR) and consitutive androstane receptors (CAR) in the cell nucleus, resulting in wide variation in the plasma efivirenz concentrations, such that a therapeutic failure or the occurence of toxic effects are to be expected. The optimal dosage of efavirenz is commonlydetermined through pharmacokinetic studies, but this is problematic in the combined use of drug with rifampicin, due to the variation in study design, method , and sample size of each study. Rthnic factors and genetic factors and genetic pohymorphism of the anzymes that metabolize efavirenz contribute to the problem of determine the optima dose of this drug. Pharmacoinetic studies with good measurement parameters and methods are still necessary as the basis for determining the optimal dose efavirenz in the Indonesia population.

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Detail Information

Series Title

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Call Number

Universa Medicine:28(3):188-201

Publisher

Grogol Jakarta : Trisakti University., 2009

Collation

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Language

English

ISBN/ISSN

1907-3062

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Edition

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Subject(s)

rifampin
TUBERCULOSIS
HIV infections
PHARMACOKINETICS

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