CYP450 genetic polymorphisms have no significant impact on the pharmacokinetics of cilostazol

Purpose: Cilostazol, a cyclic nucleotide phosphodiesterase type III inhibitor, is primarily indicated for the treatment of intermittent claudication. The metabolic pathway of cilostazol is so complex and multiple CYP450 isozymes are involved, including CYP3A, CYP2C19, CYP2C8, CYP2D6, CYP1A2 and so on. It is considered that co-administration of CYP3A or CYP2C19 inhibitors with cilostazol causes an increase in plasma concentration of cilostazol. We investigated the effects of CYP2C19, CYP2D6 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol.

Methods: Thirty-three healthy volunteers were selected and they were as extensive metabolizers (EMs) or poor metabolizers (PMs) for each isozyme according to genotype. After overnight fasting, each subject received a single oral dose of 100 mg cilostazol. Blood samples were collected up to 48 hours after drug intake, and the plasma concentrations of cilotazol were determined by using a HPLC-UV analytical method.

Results: Although relatively higher C_max and AUC values and lower CL/F value were observed in CYP2C19/CYP3A5 PM/PM group compared to CYP2C19/CYP3A5 EM/EM group, these differences were not statistically significant. There were also no significant changes in the pharmacokinetic parameters of cilostazol between different CYP2C19/CYP2D6 or CYP2D6/CYP3A5 genotype groups.

Conclusion: Genetic polymorphisms in CYP2C19, CYP2D6 and CYP3A5 did not affect the biotransformation of cilostazol.