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Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients

We investigated the effects of pharmacogenetic variations and efavirenz pharmacokinetics on inter-individual differences in the extent of CYP3A induction by efavirenz using 4β-hydroxycholesterol/cholesterol (4β-OHC/Chol) as a marker for CYP3A induction. Plasma 4β-hydroxycholesterol and cholesterol c...

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Bibliographic Details
Main Authors: Habtewold, Abiy (Author) , Riedel, Klaus-Dieter (Author) , Burhenne, Jürgen (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: The pharmacogenomics journal
Year: 2012, Volume: 13, Issue: 6, Pages: 484-489
ISSN:1473-1150
DOI:10.1038/tpj.2012.46
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/tpj.2012.46
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/tpj201246
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Author Notes:A Habtewold, W Amogne, E Makonnen, G Yimer, H Nylén, K-D Riedel, G Aderaye, L Bertilsson, J Burhenne, U Diczfalusy and E Aklillu
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Summary:We investigated the effects of pharmacogenetic variations and efavirenz pharmacokinetics on inter-individual differences in the extent of CYP3A induction by efavirenz using 4β-hydroxycholesterol/cholesterol (4β-OHC/Chol) as a marker for CYP3A induction. Plasma 4β-hydroxycholesterol and cholesterol concentrations were determined at baseline, and at the 4th, 16th and 48th week of efavirenz-based highly active antiretroviral therapy in antiretroviral therapy-naive HIV patients (n=77). Efavirenz plasma concentrations were quantified at weeks 4 and 16. CYP2B6, CYP3A5, ABCB1, UGT2B7 genotyping were done. Compared with baseline, the median plasma 4β-OHC/Chol ratio increased at the 4th (257%), 16th (291%) and 48th (165%) week (P<0.0001). CYP2B6*6 genotype significantly influenced 4β-OHC/Chol ratio at weeks 16 (P=0.02) and 48 (P=0.04) being highest in CYP2B6*6/*6>*1/*6>*1/*1. There were positive correlations between plasma efavirenz and 4β-OHC/Chol ratios (week 4: P=0.02, week 16: P=0.001). CYP3A enzyme induction by efavirenz is pronounced in CYP2B6 slow metabolizers who have high efavirenz plasma exposure.
Item Description:Published: 23 October 2012
Gesehen am 09.02.2021
Physical Description:Online Resource
ISSN:1473-1150
DOI:10.1038/tpj.2012.46

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