Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics.

ABSTRACT: To identify the genetic basis of interindividual variability in montelukast exposure, we determined its pharmacokinetics and sequenced 379 pharmacokinetic genes in 191 healthy volunteers. An intronic single nucleotide variation (SNV), strongly linked with UGT1A3*2, associated with reduced area under the plasma concentration-time curve (AUC_0-∞ ) of montelukast (by 18% per copy of the minor allele; P = 1.83 × 10^-10 ). UGT1A3*2 was associated with increased AUC_0-∞ of montelukast acyl-glucuronide M1 and decreased AUC_0-∞ of hydroxymetabolites M5R, M5S, and M6 (P < 10^-9 ). Furthermore, SNVs in SLCO1B1 and ABCC9 were associated with the AUC_0-∞ of M1 and M5R, respectively. In addition, a candidate gene analysis suggested that CYP2C8

SUBMITTER: Hirvensalo P 

PROVIDER: S-EPMC6033076 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature