Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital.
Article Details
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Hariparsad N, Nallani SC, Sane RS, Buckley DJ, Buckley AR, Desai PB
Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital.
J Clin Pharmacol. 2004 Nov;44(11):1273-81. doi: 10.1177/0091270004269142.
- PubMed ID
- 15496645 [ View in PubMed]
- Abstract
The antiretroviral agent efavirenz enhances the systemic clearance of coadministered drugs that are cytochrome P450 (CYP) 3A4 substrates. The mechanism of the apparent increase in CYP3A4 activity by efavirenz and the magnitude of change relative to other known inducers are not known. The authors tested the hypothesis that increased enzymatic activity by efavirenz entails CYP3A4 induction and activation of the human pregnane X receptor (hPXR), a key transcriptional regulator of CYP3A4. Employing primary cultures of human hepatocytes, they compared the CYP3A4 inductive effects of efavirenz (1-10 microM) to rifampin (10 microM) and phenobarbital (2 mM). A cell-based reporter assay was employed to assess hPXR activation. The authors observed that efavirenz caused a concentration-dependent CYP3A4 induction and hPXR activation. Based on the CYP3A4 activity assay, the average magnitude of induction by efavirenz (5-10 microM) was approximately 3- to 4-fold. In comparison, phenobarbital (2 mM) and rifampin (10 microM) caused a 5- and 6-fold induction, respectively.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Efavirenz Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareArtemetherEfavirenz The metabolism of Artemether can be increased when combined with Efavirenz. BoceprevirEfavirenz The serum concentration of Boceprevir can be decreased when it is combined with Efavirenz. SertralineEfavirenz The serum concentration of Sertraline can be decreased when it is combined with Efavirenz.