Summary: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 AUC0‐24from 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 AUC0‐24from 11.0 ± 2.3 &mgr;g/ml • h to 9.0 ± 2.0 &mgr;g/ml • h (p = 0.05). It is concluded that cimetidine inhibits cisapride metabolism, whereas cisapride enhances the gastrointestinal absorption of cimetidine.