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BioMed Research International
Volume 2017, Article ID 4189678, 7 pages
https://doi.org/10.1155/2017/4189678
Clinical Study

Effects of FMO3 Polymorphisms on Pharmacokinetics of Sulindac in Chinese Healthy Male Volunteers

1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China
2Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China
3Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, China
4Department of Neurology, Xiangya Hospital, Central South University, Changsha 410078, China
5Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4028, Chicago, IL 60637, USA

Correspondence should be addressed to Wei-Hua Huang; moc.621@25843ruovaedne and Zhi-Rong Tan; moc.361@rznat

Received 31 August 2016; Revised 1 November 2016; Accepted 17 November 2016; Published 26 February 2017

Academic Editor: Heiko Reutter

Copyright © 2017 Yong-Jun Tang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sulindac is a nonsteroidal anti-inflammatory drug, which is clinically used for the ailments of various inflammations. This study investigated the allele frequencies of FMO3 E158K and E308G and evaluated the influences of these two genetic polymorphisms on the pharmacokinetics of sulindac and its metabolites in Chinese healthy male volunteers. Eight FMO3 wild-type (FMO3 HHDD) subjects and seven FMO3 homozygotes E158K and E308G mutant (FMO3 hhdd) subjects were recruited from 247 healthy male volunteers genotyped by PCR-RFLP method. The plasma concentrations of sulindac, sulindac sulfide, and sulindac sulfone were determined by UPLC, while the pharmacokinetic parameters of the two different FMO3 genotypes were compared with each other. The frequencies of FMO3 E158K and E308G were 20.3% and 20.1%, respectively, which were in line with Hardy-Weinberg equilibrium ( = 0.977, = 0.944). The mean values of , , and of sulindac were significantly higher in FMO3 hhdd group than those of FMO3 HHDD group (), while the pharmacokinetic parameters except of sulindac sulfide and sulindac sulfone showed no statistical difference between the two groups. The two FMO3 mutants were in close linkage disequilibrium and might play an important role in the pharmacokinetics of sulindac in Chinese healthy male volunteers.