PURPOSE:Itopride is an effective gastroprokinetic agent mainly used for the treatment of functional dyspepsia. Flavin-containing monooxygenase 3 (FMO3) has been confirmed to be the key enzyme involved in the main itopride metabolic pathway. We investigated whether the FMO3 genotypes can affect itopride metabolism in Chinese healthy volunteers. METHODS:Twelve healthy volunteers who had been genotyped for FMO3 gene were selected to participate in our study. Volunteers were given 50 mg itopride orally and then blood samples were collected from 0 to 24 h. The plasma concentrations of itopride and itopride N-oxide were determined by HPLC-MS/MS method. RESULTS:Itopride and itopride N-oxide both exhibit FMO3 genotype-dependent pharmacokinetic profiles. The area under the plasma concentration-time curve (AUC) of itopride increased by 127.82 ± 41.99 % (P < 0.001) and the AUC of itopride N-oxide decreased by 30.30 ± 25.70 % (P < 0.05) in homozygous FMO3 hhdd subjects (n = 6) compared with the HHDD group (n = 6). The CL/F value was lower in the hhdd group than that in the HHDD group (36.60 ± 7.06 vs. 80.20 ± 15.34 L/h, P < 0.001). But no significant differences in t1/2 value and tmax of itopride and itopride N-oxide were observed between these two genotypes. CONCLUSION:The FMO3 allele can significantly affect the metabolism of itopride. The pharmacokinetic parameters of both itopride and itopride N-oxide were significantly different between these two genotypes.