白藜芦醇多相脂质体家兔体内灌胃给药的药动学

Primary study on pharmacokinetics of the resveratrol polyphase liposomes in rabbits after oral administration

目的:研究白黎芦醇多相脂质体灌胃给药后在家兔体内的药动学特征。方法:家兔一次性灌胃白黎芦醇溶液及多相脂质体后,高效液相色谱(HPLC)法测定白黎芦醇血药浓度;通过3P97程序计算药动学参数。结果:白黎芦醇溶液及多相脂质体在家兔体血药时程变化均符合二室模型。白黎芦醇多相脂质体在家兔体内消除相半衰期t1/2β为(4.4±0.3)h,曲线下面积AUC0→3为(4.6±0.6)mg·h·L-1,清除率CL为(22.0±2.8)L·kg-1·h-1,最大血药质量浓度Cmax为(3.10±0.07)mg.L-1,与白黎芦醇溶液药动学参数比较,其差异均有统计学意义,白黎芦醇溶液药动学参数t1/2β为(1.07±0.20)h,AUC0→3为(0.97±0.04)mg·h·L-1,CL为(103.3±4.0)L·kg-1·h-1,Cmax为(1.030±0.021)mg·mL-1。结论:白黎芦醇多相脂质体可延长白黎芦醇在家兔体内半衰期、增加其曲线下面积和提高最大血药浓度,降低其清除率,有利于提高白黎芦醇生物利用度。

OBJECTIVE To study the pharmaeokinetics of the resveratrol （RES） polyphase liposomes in rabbits after oral administration. METHODS Plasma concentrations of resveratrol in rabbits after oral administration were determined by HPLC. The pharmaeokinetics parameters were calculated by 3P97. RESULTS Plasma concentration-time curves of RES and RES polyphase liposomes were both fitted to two-compartment model. The pharmacokinetics parameters of RES polyphase liposomes were calculated as follows： t1/2β = （4. 37 ± 0. 34） h, AUC0→3 = （4. 6 ± 0. 6） mg·h·L^-1, CL = （22. 0 ± 2. 8 ） L·kg^-1·h^-1, Cmax = （3. 10 ± 0. 07） mg·L ^-1. The pharmacokinetics parameters of RES solution as follows： t1/2β = （1.07 ± 0. 20） h, AUC0→3 = （0. 97 ± 0. 04） mg·h·L^-1, CL = （103. 3 ± 4. 0） L· kg^- 1. h 1, Cmax = （1. 030 ± 0. 021） mg· L^- 1. There were significant difference between RES solution and RES polyphase liposomes. CONCLUSION Our present study demonstrates that compared to RES solution, RES polyphase liposomes significantly alters its pharmaeokinetics in rabbits. It can raise AUC and prolong the t1/2β and increase Cmax and reduce CL of RES in the plasma of rabbits.