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Cisapride-cimetidine interaction: enhanced cisapride bioavailability and accelerated cimetidine absorption
W Kirch1, H D Janisch, E E Ohnhaus
1First Medical Department, Christian-Albrechts-University, Kiel, F.R.G.
Therapeutic Drug Monitoring
|January 1, 1989
Summary
Cimetidine, an H2-antagonist, increases cisapride levels by inhibiting its metabolism. Cisapride, a gastrointestinal stimulant, enhances cimetidine absorption, altering drug pharmacokinetics.
Area of Science:
- Pharmacology
- Drug Interactions
- Gastrointestinal Motility
Background:
- Cisapride is a gastrointestinal motility-stimulating agent.
- Cimetidine is an H2-antagonist used to reduce stomach acid.
- Understanding drug interactions is crucial for patient safety.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between cisapride and cimetidine.
- To determine how these drugs affect each other's absorption and metabolism.
Main Methods:
- 8 healthy volunteers participated in the study.
- Subjects received oral cisapride (10 mg t.i.d.) and cimetidine (400 mg t.i.d.) separately and in combination for 1 week each.
- Steady-state pharmacokinetics of both drugs were analyzed.
Main Results:
- Cimetidine significantly increased cisapride peak plasma concentration (Cmax) and AUC0-24.
- Cisapride significantly reduced the time to peak concentration (Tmax) and AUC0-24 of cimetidine.
- Statistical significance (p < 0.05) was observed for key pharmacokinetic parameters.
Conclusions:
- Cimetidine inhibits the metabolism of cisapride, leading to higher cisapride exposure.
- Cisapride enhances the gastrointestinal absorption of cimetidine, affecting its pharmacokinetic profile.
- These findings highlight a significant pharmacokinetic interaction between cisapride and cimetidine.