Synergistic and antagonistic pharmacodynamic interaction between ranitidine and cisapride: a study on the isolated rabbit intestine.

Abstract The present study examines the pharmacodynamic interaction between the H 2 -receptor antagonist ranitidine and the prokinetic agent cisapride on the isolated rabbit intestine. Ranitidine produced a concentration-dependent contractile effect on the duodenal, ileal and ascending colon preparations, with EC 50 values of 1.35 × 10 −4 M for the duodenum, 1.2 × 10 −4 M for the ileum and 1.15 × 10 −4 M for the ascending colon. The effect of cisapride on the ranitidine contractile effect was dependent on the cisapride concentration used. Thus, cisapride, at concentrations from 10 −10 up to 5 × 10 −7 for the duodenum and the ascending colon and up to 10 −6 M for the ileum, potentiated the contractile responses of the preparations to ranitidine. However, at higher concentrations cisapride produced a non-competitive inhibition of the intestinal contractile responses to ranitidine with IC 50 values of 4.2 × 10 −5 M for the duodenum, 1.65 × 10 −5 M for the ileum and 3.2 × 10 −6 M for the ascending colon. These data show that cisapride may modify the contractile responses of the isolated rabbit intestine to ranitidine, having a potentiating effect up to a certain concentration and an antagonistic one at higher concentrations. In conclusion, co-administration of the above drugs may lead to enhanced or reduced intestinal motility.