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

The present study examines the pharmacodynamic interaction between the H-2- receptor antagonist ranitidine and the prokinetic agent cisapride on the is olated rabbit intestine. Ranitidine produced a concentration-dependent cont ractile effect on the duodenal, ileal and ascending colon preparations. wit h EC50 values of 1.35 x 10(-4) M for the duodenum, 1.2 x 10(-4) M for the i leum and 1.35 x 10(-4) M for the ascending colon. The effect of cisapride o n the ranitidine contractile effect was: dependent on the cisapride concent ration used. Thus, cisapride, at concentrations from 10(-10) up to 5 x 10(- 7) for the duodenum and the ascending colon and up to 10(-6) M for the ileu m, potentiated the contractile responses of the preparations to ranitidine. However, at higher concentrations cisapride produced a non-competitive inh ibition of the intestinal contractile responses to ranitidine with IC50 val ues of 4.2 x 10(-5) M for the duodenum, 1.65 x 10(-5) M for the ileum and 3 .2 x 10(-6) M for the ascending colon. These data show that cisapride may m odify the contractile responses of the isolated rabbit intestine to ranitid ine, having a potentiating effect up to a certain concentration and an anta gonistic one at higher concentrations. In conclusion, co-administration of the above drugs may lead to enhanced or reduced intestinal motility. (C) 20 01 Academic Press.