In vitro analysis and quantitative prediction of efavirenz inhibition of eight cytochrome P450 (CYP) enzymes: major effects on CYPs 2B6, 2C8, 2C9 and 2C19.
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Xu C, Desta Z
In vitro analysis and quantitative prediction of efavirenz inhibition of eight cytochrome P450 (CYP) enzymes: major effects on CYPs 2B6, 2C8, 2C9 and 2C19.
Drug Metab Pharmacokinet. 2013;28(4):362-71. Epub 2013 Feb 5.
- PubMed ID
- 23385314 [ View in PubMed]
- Abstract
In order to quantitatively predict drug interactions associated with efavirenz-based anti-HIV therapy, we evaluated reversible and time-dependent inhibitions of efavirenz on eight cytochrome P450 (CYP) enzymes in vitro. The present study showed that efavirenz was a potent competitive inhibitor of CYP2B6 (average K(i) = 1.68 microM in HLMs and K(i) = 1.38 microM in expressed CYP2B6) and CYP2C8 (K(i) = 4.78 microM in pooled HLMs and K(i) = 4.80 microM in HLMs with CYP2C8*3/*3 genotype). Efavirenz was a moderate inhibitor of CYP2C9 (K(i) = 19.46 microM) and CYP2C19 (K(i) = 21.31 microM); and a weak inhibitor of CYP3A (K(i) = 40.33 microM). No appreciable inhibition was observed on CYP1A2, CYP2A6 or CYP2D6. No time-dependent inhibition of the CYPs by efavirenz was observed in this study. Quantitative predictions showed that single dose of efavirenz may substantially slow the elimination of drugs predominantly cleared by CYP2B6, CYP2C19 or by both enzymes and may also lower the area under the plasma concentration time curve (AUC) of active metabolites of some pro-drugs (e.g., clopidogrel and proguanil) by up to 30%. Depending on substrates, chronic administration of efavirenz may increase the AUC of CYP2C8 and CYP2C9 substrates about 3.5-4.4-fold and 1.7-2.0-fold at steady state.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Efavirenz Cytochrome P450 1A2 Protein Humans UnknownSubstrateInhibitorDetails Efavirenz Cytochrome P450 2C19 Protein Humans UnknownInducerDetails Efavirenz Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Efavirenz Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAmodiaquineEfavirenz Efavirenz may increase the hepatotoxic activities of Amodiaquine. VoriconazoleEfavirenz The metabolism of Voriconazole can be increased when combined with Efavirenz.