Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers.
OBJECTIVE
To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men.


METHODS
Open-label, three-phase, sequential study.


METHODS
Clinical research center.


METHODS
Twelve healthy male volunteers.


METHODS
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).


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.


CONCLUSIONS
Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.
Zhao
Q
Q
Janssen Research Foundation, Titusville, New Jersey 08560-0200, USA.
Wojcik
M A
MA
Parier
J L
JL
Pesco-Koplowitz
L
L
D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics*; D019540:Area Under Curve; D020117:Cisapride / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects*; D005473:Fluoxetine / Q000493:pharmacokinetics*; D005765:Gastrointestinal Agents / Q000097:blood / Q000493:pharmacokinetics*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male
D018687:Antidepressive Agents, Second-Generation; D005765:Gastrointestinal Agents; D005473:Fluoxetine; D020117:Cisapride