Qy. Zhao et al., Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers, PHARMACOTHE, 21(2), 2001, pp. 149-157
Study Objective. To evaluate the effect of fluoxetine on the pharmacokineti
cs 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 electro
cardiograms performed at specified time points after the last morning dose
of cisapride in phases 1 and 3. Blood samples also were taken before mornin
g 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 Q
T intervals during administration of cisapride alone or with fluoxetine. Ci
sapride was well tolerated when administered alone or with fluoxetine.
Conclusion. Cisapride can be administered safely to patients receiving low
therapeutic dosages of fluoxetine.