Influence of Coadministration of Fluoxetine on Cisapride Pharmacokinetics and QTc Intervals in Healthy Volunteers

Study Objective. To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men. Design. Open‐label, three‐phase, sequential study. Setting. Clinical research center. Subjects. Twelve healthy male volunteers. Interventions. Each subject was treated according to the following sequence: baseline; phase 1 (days 1–6): cisapride 10 mg 4 times/day; washout (days 7–13); phase 2 (days 14–44): fluoxetine 20 mg/day; and phase 3 (days 45–52): cisapride 10 mg 4 times/day (days 45–51) plus fluoxetine 20 mg/day (days 45–52). Measurements and Main Results. Blood samples were drawn and 12‐lead electrocardiograms performed at specified time points after the last morning dose of cisapride in phases 1 and 3. Blood samples also were taken before morning doses on the 3rd, 4th, and 5th days of phases 1 and 3. Electrocardiograms were done at baseline and on the last day of the washout period and phase 2. Coadministration of fluoxetine significantly decreased cisapride plasma concentrations. There were no clinically significant changes in corrected QT intervals during administration of cisapride alone or with fluoxetine. Cisapride was well tolerated when administered alone or with fluoxetine. Conclusion. Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.