Efavirenz pharmacogenetics in a cohort of Italian patients

International Journal of Antimicrobial Agents
Jessica CusatoAntonio D'Avolio

Abstract

The pharmacogenetics and pharmacokinetics of efavirenz (EFV) have been widely studied, although data in the Italian population are limited. Single nucleotide polymorphisms (SNPs) in the CYP2B6 gene have been associated with increased EFV plasma concentrations and central nervous system toxicity. The aim of this work was to evaluate EFV plasma exposure according to SNPs in genes involved in drug metabolism and elimination in a cohort of Italian HIV-1-positive patients treated with EFV. Plasma samples were used to measure EFV concentrations at 12h after intake (C12) by a validated HPLC/PDA system. Whole blood was used to identify SNPs in ABCB1, MRP2, CYP2B6, CYP2A6, UGT2B7, NR1I2 (PXR), NR1I3 (CAR) and HNF4α by real-time PCR. The association between SNPs and EFV plasma levels was evaluated through non-parametric tests. Among 201 patients, the median EFV C12 was 2618.5ng/mL. No significant associations were found for MRP2, CYP2A6, UGT2B7, PXR and CAR SNPs; conversely, an association of CYP2B6 516G>T, ABCB1 3435C>T and 2677G>T, and HNF4α 975C>G polymorphisms with EFV C12 was observed. In multivariate analysis, only CYP2B6 516 TT and ABCB1 3435 TT genotypes were independently associated with an EFV C12 of >4000ng/mL (toxicity cut-of...Continue Reading

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Citations

Mar 23, 2017·Memórias do Instituto Oswaldo Cruz·Rúbia Marília de MedeirosMarilu Fiegenbaum
Dec 2, 2017·Journal of Personalized Medicine·Julie-Anne Tanner, Rachel F Tyndale
Dec 6, 2017·Pharmacogenomics·Jessica CusatoAntonio D'Avolio
May 19, 2018·Expert Opinion on Drug Metabolism & Toxicology·Gabriel StillemansLaure Elens
Jun 20, 2018·Pharmacogenomics·Sarah AllegraAntonio D'Avolio
Jun 22, 2018·Omics : a Journal of Integrative Biology·Nicholas Ekow ThomfordCollet Dandara
Sep 21, 2018·Omics : a Journal of Integrative Biology·Kevin S O'ConnellLouise Warnich
Aug 2, 2019·The Journal of Antimicrobial Chemotherapy·Pedro AyusoAndrew Owen
Apr 14, 2020·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Luz María Torres EspíndolaArnoldo Aquino-Gálvez
Sep 20, 2016·Clinical Pharmacokinetics·Andrea CalcagnoStefano Bonora
Oct 20, 2019·The Pharmacogenomics Journal·Pablo ZubiaurFrancisco Abad-Santos
Dec 15, 2020·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Srinivas Reddy PallerlaThirumalaisamy P Velavan
Apr 30, 2021·Expert Opinion on Drug Metabolism & Toxicology·Andrea CalcagnoStefano Bonora

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