Pharmacokinetics and pharmacodynamics of cisapride in patients undergoing hemodialysis

Abstract

Twenty-two patients who were receiving hemodialysis were studied in three groups of eight subjects each to assess the pharmacokinetics during the dialysis-free interval and during hemodialysis treatment and to assess the pharmacodynamics of cisapride. Cisapride and its metabolite norcisapride were measured by use of HPLC and gas chromatography, respectively. The pharmacodynamic effect of cisapride was measured by means of radionuclide gastric emptying. After a single oral dose of 20 mg the terminal half-life of cisapride was 9.6 +/- 3.3 hours, the volume of distribution was 4.8 +/- 3.3 L/kg, the total oral plasma clearance was 380 +/- 161 ml/min, the area under the curve was 1024 +/- 447 ng.hr/ml (mean +/- SD). Norcisapride only could be detected in the dialysate (0.36 +/- 0.067 mg) and was eliminated by a hemodialysis clearance of 34.7 +/- 7.9 ml/min. Cisapride reduced gastric retention from 77.6% +/- 21.1% to 43.7% +/- 18.2% of maximum filling (40 minutes after meals) and normalized the abnormal gastric emptying time in patients receiving dialysis. Cisapride dosage adjustment or substitution after hemodialysis is not necessary.