Pharmacokinetics of cisapride in normal healthy cats and recommended oral dosing regimen

Abstract

The purpose of this study was to determine the disposition of cisapride in cats following oral (PO) and intravenous (IV) administration of a single dose and the bioavailability (F) of the drug when administered as an oral capsule. 7 cats each were treated with either 1 mg/kg (IV) or 2 mg/kg (PO) after a 24 hour fast. Blood samples were collected intermittently for 36 hours following administration. Cats were studied in pairs using a random crossover design in which a cat receiving an oral dose was paired with one receiving an intravenous dose. Cisapride was detected with an HPLC assay validated for cat plasma. Drug concentration versus time curves were subjected to standard pharmacokinetic analysis. Disposition parameters were compared between PO and IV groups. Following IV administration, extrapolated peak cisapride concentration, Co, was 421.30 + 155.37 ng/ml; clearance was 0.015 + 0.0067 ml/min*kg; mean residence time (MRT) was 6.36 + 4.21 hr; and volume of distribution (Vdss) was 4.50 + 1.36 ml/kg. Cmax for the oral capsule was 73.32 + 16.59 ng/ml, MRT was 8.32 + 4.47 hr, and F was 29.0 + 22.6%. Elimination half-life was similar for both the oral and intravenous routes (T1/2(lv) = 5.19 + 3.77 hr, Tk(po) = 5.27 -+ 3.16 hr) . All cats tolerated all doses with no apparent adverse effects. Based on these data an oral dose of 1 mg/kg given every 8 hours should maintain an average concentration at steady state that lies within the published therapeutic range for people.