微透析法联用HPLC法研究复方雷公藤微乳凝胶皮肤药动学

Dermal Pharmacokinetic Study of Fufang Leigongteng Microemulsion Gel by Microdialysis Combined with HPLC

目的研究复方雷公藤微乳凝胶皮肤给药后皮肤局部药动学特征,为复方雷公藤处方开发成经皮给药制剂的可行性提供参考。方法大鼠在腹部涂抹复方雷公藤微乳凝胶后,以方中君药雷公藤的有效成分之一的雷公藤甲素为指标,利用微透析采样技术,结合高效液相色谱法测定给药后透析液中雷公藤甲素浓度,通过相对损失率的校正,计算皮肤药物质量浓度,并利用PKSolver 2.0软件对皮肤药物质量浓度和时间进行非房室模型拟合,计算相关统计矩参数。以相对累积吸收量对时间做图,计算稳态的吸收速率。结果复方雷公藤微乳凝胶给药后雷公藤甲素达峰时间为2.3 h,平均滞留时间(MRT)约为14 h,半衰期(t1/2)约8 h,稳态吸收速率为1.6μg/h。结论复方雷公藤制成微乳凝胶后其透皮性能较好,适合开发成经皮给药的微乳凝胶制剂。

OBJECTIVE To study the skin local pharmacokinetic characteristics of triptolide in Fufang Leigongteng microemulsion gel after the treatment, and to prove the feasibility of microemulsion gel as percutaneous drug delivery system for Fufang Leigongteng prescription. METHODS Having Fufang Leigongteng microemulsion gel applied to the abdomen of rats, dialysate was collected using micro dialysis sampling technology and the index compound, triptolide in the dialysate, which is one of the effective components of tripterygium wilfordii, was determined by high performance liquid chromatography method. Drug concentration in the skin was calculated through the relative loss of correction and relevant parameters of statistical moment were calculated by non-compartment model using PKSolver 2.0 software. The steady absorption rate was calculated by linear regression of cumulative release to time. RESULTS The time to peak （tmax） of triptolide was 2.3 h, which was the maximum skin concentration appeared at 2.3 h after drug administration. The mean residence time （MRT） was about 14 h and the half time （t1/2） was about 8 h. The steady absorption rate was 1.6 μg/h. CONCLUSION Fufang Leigongteng microemulsion gel has relative good percutaneous characteristics, which indicates that microemulsion gel is an ideal formation for Fufang Leigongteng prescription to cure rheumatoid arthritis.