The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam

Abstract

The effects of the benzamide cisapride (C) (8 mg) i.v. have been compared to placebo (P) in a double blind randomised study. The effects on gastric emptying, the absorption and effects of oral diazepam, and BP and pulse were observed. Cisapride increased the rate of gastric emptying of 500 ml liquid containing diazepam 10 mg (t 1/2 C: 7.4 min, P: 14.9 min). The initial rate of absorption of diazepam contained in the drink was increased by C (AUC 0-1 h C: 328 micrograms h l-1, P: 253 micrograms h l-1, but there was no change in overall bioavailability. This change in diazepam kinetics was associated with a significantly greater impairment in reaction time in the first 45 min after drinking but not in self rated sedation. Cisapride produced a significant tachycardia (e.g. after 10 min C: 82 beats/min, P: 69 beats/min) which probably reflects a peripheral vasodilator action. Cisapride may therefore alter the pharmacokinetics and dynamics of concurrently administered drugs.