桂利嗪胃内滞留漂浮型缓释片犬体内的药动学

Pharmacokinetics of the cinnarizine floating sustained-release tablet in dogs

目的：建立犬血浆中桂利嗪浓度的HPLC测定方法,并用于桂利嗪胃内滞留漂浮型缓释片剂犬体内药动学研究及其缓释作用评价。方法：血浆经正己烷-氯仿（3∶2）提取,采用色谱柱为Spherisorb ODS柱（150 mm×4.6 mm,5μm）,流动相为：0.04%三乙胺NH4H2PO4（0.01 mol.L-1,pH4.7）水溶液-乙腈（40∶60）,流速为：0.8 mL.min-1,进样量为：20.0μL,对样品进行分析。结果：桂利嗪的线形范围为15~1 500 ng.mL-1,相对回收率分别为86.7%~101.2%,绝对回收率分别为78.5%~88.9%,日内RSD〈3.26%,日间RSD〈6.38%。犬服用桂利嗪胃内滞留漂浮型缓释片、普通凝胶骨架缓释片和普通片后的主要药动学参数：Tmax分别为3.48,2.98和0.83 h,采用梯形法计算AUC分别为5 460.7,4 019.5和2 524.4ng.h.mL-1。桂利嗪胃内滞留漂浮型缓释片和普通凝胶骨架缓释片相对于普通片的生物利用度分别为237.72%和155.89%。结论：该法灵敏准确,测定结果可靠,适用于桂利嗪犬药动学研究,统计分析表明桂利嗪胃内滞留漂浮型缓释片较普通凝胶骨架缓释片和普通片具有一定的缓释作用,可以大幅度提高桂利嗪的生物利用度。

Objective：To establish the HPLC method for detecting cinnarizine concentration in dog plasma,and evaluate the pharmacokinetics and the sustained-release performance of the cinnarizine floating sustained-release tablet by this method.Methods： Plasma was extracted by n-hexane-chloroform（3∶2）.The analyzing method included an HPLC column of spherisorb ODS（150mm × 4.6mm,5μm）;a mobile phase of 0.04% triethylamine NH4H2PO4（0.01mol·L-1,pH4.7） in aqueous solution-acetonitrile（40∶60）,and a flow rate of 0.8 mL·min-1（injection volume 20.0μL）.Results： The linear range of cinnarizine was 15~1500ng·mL-1;the relative recoveries were 86.7%~101.2%;the absolute recoveries were 78.5%~88.9%;the intraday RSD was less than 3.26%;the interday RSD was less than 6.38%.The main pharmacokinetic parameter Tmax was 3.48,2.98 or 0.83h,and the corresponding AUC value was 5460.67,4019.5 or 2524.4ng·h·mL-1 by using the trapezoidal method,after taking floating sustained-release tablets,gel-matrix sustained-release tablets or conventional tablets.The bioavailability of the cinnarizine floating sustained-release tablet or the gel-matrix sustained-release tablet was 237.72% or 155.89%,respectively,as compared with the conventional tablet.Conclusion： The method is sensitive,accurate and reliable in the measurements of dog pharmacokinetic study.The floating sustained-release tablet has a reliable sustained-release effect,resulting in a statistically higher bioavailability than those of the gel-matrix sustained-release tablet and the conventional tablet.