Correlates of Efavirenz Exposure in Chilean Patients Affected With Human Immunodeficiency Virus Reveals a Novel Association With a Polymorphism in the Constitutive Androstane Receptor
Copyright policy )Correlates of Efavirenz Exposure in Chilean Patients Affected With Human Immunodeficiency Virus Reveals a Novel Association With a Polymorphism in the Constitutive Androstane Receptor
To explore the effect of demographics and single-nucleotide polymorphisms in cytochrome P450 (CYP) 2B6, 2A6, UDP-glucuronosyltransferase (UGT) 2B7, and the constitutive androstane receptor (CAR) genes on efavirenz pharmacokinetics in a Chilean cohort affected with human immunodeficiency virus.Timed plasma samples obtained throughout the dosing interval were analyzed for efavirenz concentrations with liquid chromatography/tandem mass spectrometry. DNA from whole-blood samples was used for genetic analysis. Data were analyzed using a Mann-Whitney statistical test; furthermore, a Pearson or Spearman correlation was used. A multivariate analysis was then conducted using multiple linear regression by best subset analysis.Overall 219 patients were included, 208 patients had measurable efavirenz levels and available genetic samples. The overall median (interquartile range) of efavirenz concentration was 2.6 (2.1-3.7) mcg/mL. In multivariate regression analysis, CYP2B6 516G>T (P T (P = 0.002) were significantly related to efavirenz plasma concentrations.This novel association between CAR rs2307424 and efavirenz plasma concentrations now requires validation in other cohorts.
- University of Liverpool United Kingdom
- University of Ottawa Canada
- The Ottawa Hospital Research Institute Canada
- University of Chile Chile
Cyclopropanes, Male, Anti-HIV Agents, Receptors, Cytoplasmic and Nuclear, HIV Infections, Polymorphism, Single Nucleotide, smoking, Cohort Studies, Cytochrome P-450 CYP2A6, Humans, genetics, Chile, Glucuronosyltransferase, Constitutive Androstane Receptor, constitutive androstane receptor, CYP2B6, efavirenz, Oxidoreductases, N-Demethylating, Hispanic or Latino, Benzoxazines, Cytochrome P-450 CYP2B6, Alkynes, Female, Aryl Hydrocarbon Hydroxylases, polymorphisms, pharmacokinetics
Cyclopropanes, Male, Anti-HIV Agents, Receptors, Cytoplasmic and Nuclear, HIV Infections, Polymorphism, Single Nucleotide, smoking, Cohort Studies, Cytochrome P-450 CYP2A6, Humans, genetics, Chile, Glucuronosyltransferase, Constitutive Androstane Receptor, constitutive androstane receptor, CYP2B6, efavirenz, Oxidoreductases, N-Demethylating, Hispanic or Latino, Benzoxazines, Cytochrome P-450 CYP2B6, Alkynes, Female, Aryl Hydrocarbon Hydroxylases, polymorphisms, pharmacokinetics
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