犬血浆中牡荆素鼠李糖苷的测定及益心酮缓释片药动学研究

Determination of vitexin-rhamnoside in Beagle dog plasma and preliminary pharmacokinetics of Yixintong sustained release tablets

目的:建立测定犬血浆中牡荆素鼠李糖苷的HPLC法,初步研究益心酮缓释片在Beagle犬体内的药动学。方法:应用自身对照设计实验法,用反相高效液相色谱法测定单剂量口服益心酮缓释片(2片×288 mg/片)和市售普通片(4片×144 mg/片)后,Beagle犬血浆中牡荆素鼠李糖苷的浓度,应用非隔室模型统计矩方法和3p87程序对药动学参数进行分析。结果:益心酮缓释片和普通片口服后在Beagle犬体内过程可分别用单室和双室模型描述;药动学参数为:口服普通片:T1/2=8.94 h,Tmax=1 h,AUC0-∞=5 880.4 ng.h.mL-1,MRT=6.1 h;口服缓释片:T1/2=5.22 h,Tmax=4 h,AUC0-∞=6 792.75 ng.h.mL-1,MRT=8.4 h,相对生物利用度为115.5%。结论:自制缓释片在犬体内表现出了缓释特性。

Objective： To develop an HPLC method to determine vitexin-rhamnoside in plasma of Beagle dogs and study the pharmacokinetics and bioavailability of Yixintong sustained release tablets in Beagle dogs. Method： A newly-developed HPLC method using C18 column and methanol-acetonitrile-tetrahydrogenfuran-0. 5% acetic acid （1： 1： 19.4： 78. 6） as mobile phase was validated, and then was employed to determine vitexin-rhamnoside in plasma of Beagle dogs after oral administration of Yixintong sustained release tablets and general tablets. The main pharmacokinetic parameters were estimated by pharmacokinetic program 3p87. The non-compart- mental pharmacokinetic parameters were also calculated on basis of the statistic moment theory. Result： The pharmacokinetic profiles of Yixintong sustained release tablets and the general tablets were fitted to a one-and two-compartment open model, respectively. The T1/2, Tmax, AUC00-∞ and MRT for Yixintong sustained release tablets were 5.22 h, 4.0 h, 6 792.75 ng · h ·mL^- 1 and 8.4 h, respectively, compared with 8.94 h, 1.0 h, 5 880. 4 ng ·h ·mL^-1 and 6. 1 h for the general tablets. The relative bioavailability of the Yixintong sustained release tablets was 115.5% in Beagle dogs. Conclusion： The sustained-release characteristic of Yixintong sustained release tablets were confirmed by pharmacokinetic study.