Effects of single-nucleotide polymorphisms of FMO3 and FMO6 genes on pharmacokinetic characteristics of sulindac sulfide in premature labor

This study aimed to investigate the effects of polymorphisms of the flavin-containing mono-oxygenase 3 (FMO3) and flavin-containing mono-oxygenase 6 (FMO6) genes on the pharmacokinetics of sulindac sulfide, the active metabolite of sulindac, in patients with preterm labor. Ten single-nucleotide polymorphisms (SNPs) were genotyped, and plasma sulindac sulfide concentrations were measured at 0, 1.5, 4, and 10 hours after drug administration. The area under the curve from time 0 to the last sampling time point (AUC_last) for sulindac sulfide was obtained. The AUC_last of sulindac sulfide was significantly higher in patients with variant-type homozygotes of FMO3 (rs909530) than those with ancestral alleles or heterozygotes. FMO3 (rs2266780) was in complete linkage disequilibrium with FMO6 (rs7885012), and there was marginal significance between the genotypes (P = 0.049). From multiple linear regression models, FMO3 (rs909530) was found to have significant influence on the AUC_last of sulindac sulfide after adjusting for gestational age, weight, and all studied SNPs. The predictive contribution of rs909530 to the variability of sulindac sulfide AUC_last was 27.0%. In conclusion, the results of this study could help clinicians predict the efficacies and side effects of sulindac in the development of individualized treatment of patients with preterm labor.