Effect of CYP2C9 Polymorphisms on the Pharmacokinetics of Indomethacin During Pregnancy.

ABSTRACT:

Background and objective

Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women.

Methods

Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. DNA was isolated from subject blood and buccal smear samples. Subjects were grouped by genotype for comparisons of pharmacokinetic parameters.

Results

For subjects with the *1/*2 genotype, the mean steady-state apparent oral clearance (CL/F_ss) of indomethacin was 13.5 ± 7.7 L/h (n = 4) and the mean metabolic ratio (AUC_DMI/AUC_indomethacin) was 0.291 

SUBMITTER: Shah M 

PROVIDER: S-EPMC6380929 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature