Pharmacokinetics of cisapride in the horse.

The study investigates how the drug cisapride is metabolized and circulated within horses after it is administered through intragastric (i.g.) and intravenous (i.v.) means. It found that, despite significant variance between individuals, cisapride is absorbed rapidly, yet only about half the orally administered dose enters the bloodstream.

Objective and Methodology

• The objective of the study was to understand the pharmacokinetics (how a drug is absorbed, distributed, metabolized, and excreted) and absolute bioavailability (percentage of the administrated drug that reaches the systemic circulation) of cisapride in horses.
• The researchers experimented on five adult, healthy horses. The horses were given single doses of 0.1 mg/kg, 0.2 mg/kg, and 0.4 mg/kg of cisapride through intragastric (i.g.) administration in an open, randomized manner on different occasions with washout intervals of at least 48 hours.
• Four of these horses were also given a single intravenous (i.v.) dose of 0.1 mg/kg of cisapride.
• Jugular venous blood samples were collected periodically for 24 hours after each drug administration. The plasma cisapride concentrations were measured using high-performance liquid chromatography.

Findings

• The results revealed high inter-individual variability in pharmacokinetic parameters. This means that the drug behavior varied significantly between individual horses.
• Despite the variability, the mean values for systemic clearance (CI) and steady-state volume of distribution (Vss) were found to be 494 (43.6) mL/h/kg and 1471 (578) mL/kg, respectively.
• The rate of cisapride absorption was quite rapid. However, only about half the intragastrically administered dose was absorbed into the systemic circulation.
• The average terminal half-life (the time taken for the concentration of the drug to reduce to half its initial value) calculated over the three i.g. doses was 2.06 hours. On the other hand, the half-life for intravenous administration was slightly higher, 2.12 hours.
• Interestingly, the pharmacokinetic behavior of cisapride was found to be independent of the i.g. administered dose, ranging from 0.1 mg/kg to 0.4 mg/kg. This implies that changing the dosage does not significantly affect the rate at which the drug is metabolized and eliminated from the body.

Implications

• The findings of this study provide valuable insights into how cisapride behaves within the bodies of horses, contributing to more effective treatment plans involving this drug.
• The unexpectedly low rate of absorption of cisapride when administered orally and the independence of its pharmacokinetics from dosage level might influence the way it is used for treatment, potentially leading towards preference for intravenous administration.