کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3358440 1591757 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Efavirenz pharmacogenetics in a cohort of Italian patients
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Efavirenz pharmacogenetics in a cohort of Italian patients
چکیده انگلیسی


• Efavirenz (EFV) concentrations are associated with CYP2B6, ABCB1 and HNF4α SNPs.
• CYP2B6 516 TT and ABCB1 3435 TT genotypes predict EFV concentrations >4000 ng/mL.
• Genetic patterns using different SNPs may be useful in optimising EFV dosing.

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 12 h 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 2618.5 ng/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 >4000 ng/mL (toxicity cut-off). This study confirmed the role of CYP2B6 and ABCB1 polymorphisms, showed a relationship with HNF4α, and the lack of association of CYP2A6, UGT2B7, NR1I2 and NR1I3 SNPs on EFV plasma exposure. Data regarding some of the studied SNPs are the first obtained in an Italian cohort of HIV patients and lead to a global vision about EFV pharmacogenetics.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 47, Issue 2, February 2016, Pages 117–123
نویسندگان
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