目的 考察生川烏瓜蔞不同配伍比例醇提液中烏頭類生物堿在大鼠體內(nèi)的藥動(dòng)學(xué)研究,比較瓜蔞對其藥動(dòng)學(xué)行為的影響。方法 建立靈敏、專屬、快速的測定大鼠血漿中6種烏頭類生物堿的液相色譜-串聯(lián)質(zhì)譜方法。大鼠隨機(jī)分為3組,分別ig生川烏與瓜蔞1:0、6:1、1:6配伍醇提液,在不同的時(shí)間點(diǎn)采血分析,經(jīng)DAS 2.0軟件計(jì)算主要藥動(dòng)學(xué)參數(shù)。結(jié)果 烏頭堿、次烏頭堿、新烏頭堿的藥動(dòng)學(xué)參數(shù)t_max和t_1/2發(fā)生了顯著變化,且變化趨勢基本一致,在生川烏與瓜蔞6:1配伍組t_max顯著減小(P<0.05),生川烏與瓜蔞1:6配伍組t_max顯著增加(P<0.01、0.001),且t_1/2顯著降低(P<0.05、0.01),提示生川烏與瓜蔞不同配伍比例影響了3種生物堿的吸收和消除過程。結(jié)論 生川烏與瓜蔞配伍影響了烏頭類生物堿的藥動(dòng)學(xué)過程,配伍比例是其配伍禁忌的重要條件。

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 Blood samples were withdrawn at different time points and analyzed.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.

國家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃項(xiàng)目(2011CB505300,2011CB505302);天津市高等學(xué)校科技發(fā)展基金計(jì)劃項(xiàng)目(20140208)