1. Correlates of efavirenz exposure in Chilean patients affected with human immunodeficiency virus reveals a novel association with a polymorphism in the constitutive androstane receptor.
- Author
-
Cortes CP, Siccardi M, Chaikan A, Owen A, Zhang G, and la Porte CJ
- Subjects
- Alkynes, Anti-HIV Agents blood, Anti-HIV Agents pharmacokinetics, Aryl Hydrocarbon Hydroxylases genetics, Benzoxazines blood, Benzoxazines pharmacokinetics, Chile, Cohort Studies, Constitutive Androstane Receptor, Cyclopropanes, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Female, Glucuronosyltransferase genetics, HIV Infections blood, HIV Infections enzymology, Hispanic or Latino, Humans, Male, Oxidoreductases, N-Demethylating genetics, Polymorphism, Single Nucleotide, Anti-HIV Agents administration & dosage, Benzoxazines administration & dosage, HIV Infections drug therapy, HIV Infections genetics, Receptors, Cytoplasmic and Nuclear genetics
- Abstract
Objective: 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., Methods: 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., Results: 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 < 0.0001) and CAR rs2307424 C>T (P = 0.002) were significantly related to efavirenz plasma concentrations., Conclusion: This novel association between CAR rs2307424 and efavirenz plasma concentrations now requires validation in other cohorts.
- Published
- 2013
- Full Text
- View/download PDF