泽泻与复方花旗泽仁给药后泽泻醇A-24-醋酸酯在大鼠体内的比较药代动力学研究

Pharmacokinetic Study of Alisol A-24-Acetate in Rats Intervened by Rhizoma alismatis and Huaqizeren

目的:建立HPLC-MS/MS测定大鼠血浆中泽泻醇A-24-醋酸酯浓度的方法,比较单味药泽泻与复方花旗泽仁中有效成分——泽泻醇A-24-醋酸酯在大鼠体内的药代动力学差异,评价配伍对泽泻醇A-24-醋酸酯的动力学影响。方法:雄性SD大鼠12只,随机分为泽泻组与花旗泽仁组,灌胃给药后在不同时间点进行采血,采用DAS2. 0数据处理软件的非房室模型法(统计矩法)计算药代动力学参数。结果:泽泻单独给药时泽泻醇A-24-醋酸酯最大浓度(Cmax)为(71. 88±13. 43)μg/L;达峰时间(T_(max))为0. 50 h;半衰期(t_(1/2))为(6. 065±2. 246) h;浓度-时间曲线下面积(AUC0-t)为(350. 60±47. 70)μg/(L·h);平均驻留时间(MRT0-t)为(7. 644±0. 692) h;清除率(CL)为(0. 397 7±0. 056 9)L/(h·kg);配伍后泽泻醇A-24-醋酸酯Cmax为(67. 46±22. 10)μg/L; T_(max)为1 h; t_(1/2)为(5. 543±1. 515) h; AUC0-t为(492. 50±69. 79)μg/(L·h); MRT0-t为(7. 667±1. 127) h; CL为(0. 288 5±0. 047 4) L/(h·kg)。结果:花旗泽仁组中泽泻醇A-24-醋酸酯的浓度-时间曲线下面积和清除率与泽泻组比较有显著性差异(P <0. 05),其他参数比较均无显著性差异(P> 0. 05)。结论:配伍后泽泻醇A-24-醋酸酯药时曲线依然存在明显的双峰现象;泽泻配伍为花旗泽仁可使泽泻醇A-24-醋酸酯在大鼠体内起效时间延长,吸收程度增加,血浆清除率降低。

Objective ： To establish HPLC - MS/MS method for the determination of alisol A - 24 - acetate in rats＇ plasma, and to compare the pharmacokinetic differences of alisol A -24 - acetate from single herb of Zexie （Rhizoma alismatis） and from Huaqizeren formula, thus to evaluate the effect of compatibility on the ki- netics of alisol A - 24 - acetate. Methods ： 12 male SD rats were randomly divided into Zexie group and Hua- qizeren group. Blood samples were collected at different time points after gavage administration. The pharma-cokinetic parameters were calculated by DAS 2.0 software（ statistics moment method）. concentration of alisol A - 24 - acetate（C ） was （71.88 ±13.43） μg/L, the peak Results ： The maximum time（T ） was0.50 h and the half life time （ t1/2 ） was （6. 065 ± 2. 246 ） h; the area under the concentration - time cure-e （ AUG0 -t ） was （350.60 ±47.70） μg/（L · h） ; mean residence time（MRT0-t） was （7. 644 ±0. 692） h; clearance rate （CL） was （0. 397 7 ±0. 056 9）L/（h · kg）; after the compatibility, C of alisol A -24 -acetate was （67.46 ±22.10） μg/L; T was 1 h; t1/2 was （5. 543 ± 1. 515） h; AUG0-t was （492.50 ± 69. 79） μg/（L · h） ; MRT0-t was （7.667 ±1. 127） h; CL was （0.288 5 ±0.047 4） L/（h · kg）. Results： AUG0-t and CL of alisol A - 24 - acetate in Huaqizeren group were significantly different from those in the Zexie group （P 〈 0.05）, and no significant differences were found in temps of other parameters （P 〉 0.05 ）. Conclusion ： There is still a phenomenon of bimodal distribution in the curve of alisol - A - 24 - acetate after the compatibility. Compatibility of Rhizoma alismatis makes the effect of alisol A - 24 - acetate longer, increases its absorption and reduces its plasma clearance.