title: Effects of single-nucleotide polymorphisms of FMO3 and FMO6 genes on pharmacokinetic characteristics of sulindac sulfide in premature labor.
abstract: 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 AUClast 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.
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea (S.P., N.R.L., K.E.L., J.Y.P., H.S.G.); and Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, Seoul, Korea (Y.J.K.).
authors.forename: Sunny
authors.initials: S
authors.lastname: Park
authors.forename: Na Ra
authors.initials: NR
authors.lastname: Lee
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Park
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Gwak
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D005838:Genotype; D005865:Gestational Age; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D007752:Obstetric Labor, Premature / Q000235:genetics*; D010105:Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D013467:Sulindac / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D013467:Sulindac; C025462:sulindac sulfide; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)