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Pharmacokinetics of cisapride in horses after intravenous and rectal administration
G Cook1, M G Papich, M C Roberts
1Department of Food Animal and Equine Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Objectives:
To determine the i.v. pharmacokinetics of cisapride and measure systemic absorption after rectal administration.
Animals:
5 healthy adult mares (380 to 610 kg).
Procedure:
Cisapride was administered, i.v., 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 administering the mixture into the rectum. After each drug administration, a series of blood samples were collected. Plasma was obtained and analyzed by high-performance liquid chromatography to determine cisapride concentration profiles after each drug administration.
Results:
After i.v. administration, peak plasma concentration was 221.4 ng/ml and harmonic mean half-life was 1.9 hours. Rectal absorption of cisapride was negligible. Cisapride was detected in plasma from only 3 of 5 horses for which mean systemic availability was 1.23%. Mean maximal plasma concentration after rectal administration of cisapride was 13.5 ng/ml.
Conclusion And Clinical Relevance:
After i.v. administration of cisapride, plasma concentration is high for approximately 2 hours. Cisapride mixed with 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.