Evaluation of pharmacokinetic interaction of cilostazol with metoclopramide after oral administration in human

Background: Metoclopramide is mainly metabolized by CYP2D6, CYP3A4, CYP2C19, and CYP1A2 enzymes, while cilostazol is also metabolized by CYP3A4, CYP2C19, and CYP1A2 enzymes. Methods: This was a randomized, two-phase cross-over pharmacokinetic study separated by a 4-week wash-out time period, 12 healthy non-smoking volunteers received metoclopramide 20 mg as a single oral dose and after 4 weeks, cilostazol 100 mg twice daily for 4 days then with metoclopramide 20 mg on test day. Serial blood samples were analyzed by using a validated high-performance liquid chromatography-ultraviolet method to determine maximum plasma drug concentration (C_max)_, time to reach (T_max), and area under the curve (AUC_0-∞) of metoclopramide. Results: Cilostazol increased the mean C_max, AUC_0-∞ and half-life (T_1/2) of metoclopramide by 6%, 27% and by 0.79 %, respectively. In addition, T_max of metoclopramide was delayed by cilostazol. Conclusion: The results showed delayed T_max of metoclopramide by cilostazol, which could lead to the conclusion that cilostazol affects the absorption of metoclopramide. Both drugs when necessary to administer together must not be administered at the same time especially when given in gastroparesis patients.