目的 考察生川乌瓜蒌不同配伍比例醇提液中乌头类生物碱在大鼠体内的药动学研究,比较瓜蒌对其药动学行为的影响。方法 建立灵敏、专属、快速的测定大鼠血浆中6种乌头类生物碱的液相色谱-串联质谱方法。大鼠随机分为3组,分别ig生川乌与瓜蒌1:0、6:1、1:6配伍醇提液,在不同的时间点采血分析,经DAS 2.0软件计算主要药动学参数。结果 乌头碱、次乌头碱、新乌头碱的药动学参数t_max和t_1/2发生了显著变化,且变化趋势基本一致,在生川乌与瓜蒌6:1配伍组t_max显著减小(P<0.05),生川乌与瓜蒌1:6配伍组t_max显著增加(P<0.01、0.001),且t_1/2显著降低(P<0.05、0.01),提示生川乌与瓜蒌不同配伍比例影响了3种生物碱的吸收和消除过程。结论 生川乌与瓜蒌配伍影响了乌头类生物碱的药动学过程,配伍比例是其配伍禁忌的重要条件。

Objective To study pharmacokinetics of aconitum alkaloids from ethanol extracts of Aconiti Radix and Trichosanthis Fructus in different compatibility ratios after oral administration to rats, and compare the influence of Trichosanthis Fructus on pharmacokinetic characterization of Aconiti Radix. Methods A sensitive, selective and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for simultaneous determination of the six aconitum alkaloids in rat plasma. Rats were randomly divided to three groups, and were given ethanol extracts of Aconiti Radix and Trichosanthis Fructus in different compatibility ratios (1:0, 6:1 and 1:6), respectively. Blood samples were withdrawn at different time points and analyzed. Main pharmacokinetic parameters were calculated using DAS 2.0 Software Package. Results Pharmacokinetic parameters including t_max and t_1/2 of aconitine, hypaconitine, and mesaconitine varied significantly after compatibility, with almost the same variation trend. Compared with Aconiti Radix group, t_max of aconitine, hypaconitine, and mesaconitine decreased significantly (P < 0.05) in group of Aconiti Radix and Trichosanthis Fructus in compatibility ratio of 6:1, while increased significantly (P < 0.01, 0.001) in group of Aconiti Radix and Trichosanthis Fructus in compatibility ratio of 1:6. T_1/2 of aconitine, hypaconitine, and mesaconitine decreased significantly (P < 0.05, 0.01) in group of Aconiti Radix and Trichosanthis Fructus in compatibility ratio of 1:6. The compatibility of Aconiti Radix and Trichosanthis Fructus could affect absorption and elimination of the three aconitum alkaloids. Conclusion Aconiti Radix in compatibility with Trichosanthis Fructus led to pharmacokinetic alteration of the aconitum alkaloids, and compatibility ratio is an important condition for the incompatibility of Aconiti Radix and Trichosanthis Fructus.

国家重点基础研究发展计划项目(2011CB505300,2011CB505302);天津市高等学校科技发展基金计划项目(20140208)