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

• Verfasst von: Habtewold, Abiy [VerfasserIn]
• Verfasst von: Riedel, Klaus-Dieter [VerfasserIn]
• Verfasst von: Burhenne, Jürgen [VerfasserIn]
• Titel: Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients
• Verf.angabe: A Habtewold, W Amogne, E Makonnen, G Yimer, H Nylén, K-D Riedel, G Aderaye, L Bertilsson, J Burhenne, U Diczfalusy and E Aklillu
• Jahr: 2013
• Jahr des Originals: 2012
• Umfang: 6 S.
• Fussnoten: Published: 23 October 2012 ; Gesehen am 09.02.2021
• Titel Quelle: Enthalten in: The pharmacogenomics journal
• Ort Quelle: Basingstoke : Nature Publishing Group, 2001
• Jahr Quelle: 2013
• Band/Heft Quelle: 13(2013), 6, Seite 484-489
• ISSN Quelle: 1473-1150
• DOI: doi:10.1038/tpj.2012.46
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1747169625

Abstract

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.