Cisapride Pharmacokinetic Studies

Objective: 1. A HPLC-FLUOR method with detection was developed and validated to de ermine cisapride in plasma, to study the pharmacokinetics profile and bioequivalence of cispride in Chinese healthy volunteers. 2. To study the pharmacokinetics profiles of cisapride co ribined with omeprazole in rabbits. Methods: The study was conducted in a two-way cross-over design, as a single does randomized trial. Each volunteer was orally given cisapride tablet and capsule. Eight rabbits were divided into cispride group and in co ribination with omeprazole group. Plasma samples were assayed for cisapride using high- pe formance liquid chromatography method with fluorescence detection. The ph irmacokinetics pharmeters as well as relative bioavailability were measured. To compare the difference of two groups and realize the case of drugs interaction under the condition of co nbination with omeprazo]e. Results: the concentration-time curves of two formulations were conformed to a two-compartment open model with first-order absorption. The main phirmacokinetic pharmeters of capsule or tablet were as follows: ~ were 79.87?1.26 and 75.24?2.85 it gIL; Tmax were 1.50+0.21 and 1.54?.33 h; AUC036 were 777.05?28.47 and 77 1.61?29.01 it gIL h; T112~ were 10.07?.81 and 9.79?.27 h respectively. There were no significant difference between the two formulations (P>0.05). The relative bioavailability of cisapride capsule was 101.12?.89%. The pharmacokinetics parameters of single-does group and combination-does group of rabbits were as follow: ~ were 26.21?.77 and 28.32?.79 It g/L; AUC024 were 217.61+48.25 and 247.91?1.26 It gIL h; T112~ were 8.20+0.67 and 8.8 1?.50 h respectively; Tiiia~ were all 0.92?.17 h. There were no significant different between these parameters. Conclusion: A HPLC-FLUOR method that determine cuapride in plasma is sensitive, accurate and reliable. Domestic cisapride capsule and tablet were bioequivalent. The pharmacokinetics profiles of single-does cisapride will not be chtnged by co-administered omeprazole.