Cisapride-cimetidine interaction: enhanced cisapride bioavailability and accelerated cimetidine absorption.
The pharmacokinetic interaction between the gastrointestinal motility-stimulating substance cisapride and the H2-antagonist cimetidine was examined in 8 healthy volunteers (25 +/- 2 years of age). Steady-state kinetics of both substances were investigated after separate 1-week treatments of oral cisapride, 10 mg t.i.d., cimetidine, 400 mg t.i.d., and the two drugs combined. Cimetidine increased the cisapride peak plasma concentration from 58 +/- 25 ng/ml to 84 +/- 19 ng/ml (p = 0.01) and AUC0-24 from 509 +/- 289 ng/ml.h to 738 +/- 148 ng/ml.h (p = 0.02). Cisapride shortened the time to the peak concentration of cimetidine from 1.3 +/- 0.6 h to 0.6 +/- 0.2 h (p = 0.005) and reduced the cimetidine AUC0-24 from 11.0 +/- 2.3 micrograms/ml.h to 9.0 +/- 2.0 micrograms/ml.h (p = 0.05). It is concluded that cimetidine inhibits cisapride metabolism, whereas cisapride enhances the gastrointestinal absorption of cimetidine.
Kirch
W
W
First Medical Department, Christian-Albrechts-University, Kiel, F.R.G.
Janisch
H D
HD
Ohnhaus
E E
EE
van Peer
A
A
D000328:Adult; D001682:Biological Availability; D002927:Cimetidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D020117:Cisapride; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*
D010880:Piperidines; D002927:Cimetidine; D020117:Cisapride