PHARMACOKINETICS OF CISAPRIDE IN HORSES AFTER INTRAVENOUS AND RECTAL ADMINISTRATION

Objectives-To determine the IV pharmacokinetics of cisapride and measu re systemic absorption after rectal administration. Animals-5 healthy adult mares (380 to 610 kg), Procedure-Cisapride was administered, IV, at a dosage of 0.1 mg/kg of body weight. In the same horses, after a 1-week washout period, cisapride was administered rectally at a dosage of 1 mg/kg by mixing crushed tablets with propylene glycol and admini stering the mixture into the rectum. After each drug administration, a series of blood samples were collected. Plasma was obtained and analy zed by high-performance liquid chromatography to determine cisapride c oncentration profiles after each drug administration. Results-After IV administration, peak plasma concentration was 221.4 ng/ml and harmoni c mean half-life was 1.9 hours. Rectal absorption of cisapride was neg ligible. Cisapride was detected in plasma from only 3 of 5 horses for which mean systemic availability was 1.23%. Mean maximal plasma concen tration after rectal administration of cisapride was 13.5 ng/ml. Concl usion and Clinical Relevance-After IV administration of cisapride, pla sma concentration is high for approximately 2 hours. Cisapride mixed w ith propylene glycol and administered rectally at a dosage of 1 mg/kg is poorly and incompletely absorbed, Thus, cisapride is not clinically useful for rectal administration in horses.