Therapeutic drug monitoring · 2013
Correlates of efavirenz exposure in Chilean patients affected with human immunodeficiency virus reveals a novel association with a polymorphism in the constitutive androstane receptor.
Клиническое исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Cortes Claudia P, Siccardi Marco, Chaikan Ammara, Owen Andrew, Zhang Guijun, la Porte Charles J L
Аннотация
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.
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.
Предметные рубрики MeSH
AlkynesAnti-HIV AgentsAryl Hydrocarbon HydroxylasesBenzoxazinesChileCohort StudiesConstitutive Androstane ReceptorCyclopropanesCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6FemaleGlucuronosyltransferaseHIV InfectionsHispanic or LatinoHumansMaleOxidoreductases, N-DemethylatingPolymorphism, Single NucleotideReceptors, Cytoplasmic and Nuclear