微透析联用反相高效液相色谱研究白芥子涂方皮肤药动学

目的研究白芥子涂方皮肤给药后皮肤局部药动学特征,为白芥子涂方贴敷预防和治疗哮喘的药物作用机制研究提供参考。方法大鼠在体贴敷白芥子涂方后,以方中君药白芥子的有效成分芥子碱硫氰酸盐为指标,利用微透析采样技术,结合反相高效液相色谱分析,测定白芥子涂方贴敷给药后透析液的药物质量浓度,通过相对损失率的校正,计算皮肤药物质量浓度,并利用Kinetica 4.4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。结果白芥子涂方贴敷给药后芥子碱硫氰酸盐达峰时间为1.5 h,平均滞留时间(MRT)约为22 h,半衰期(t1/2)约15 h,稳态吸收速率为13.65μg/h。结论微透析取样技术结合反相高效液相色谱分析可研究白芥子涂方给药后的皮肤药动学,给药后的皮肤药动学行为与其临床作用特点相一致,可为阐明白芥子涂方贴敷预防和治疗哮喘的药物作用机制提供研究手段。

Dermal pharmacokinetic study of Baijiezi Tufang by microdialysis combined with RP-HPLC

Objective Dermal pharmacokinetics of Baijiezi Tufang was studied to provide the reference for explaining the drug mechanism of its asthma prevention and cure.Methods Baijiezi Tufang was applied percutaneously to rats in vivo.Sinapine thiocyanate was used as index and the samples were extracted by microdialysis and detected by reverse phase high performance liquid chromatography(RP-HPLC).The dermal concentration was corrected by relative loss rate,the relationship between concentration and time was analyzed by Kinetica 4.4,and the statistical moment parameters were calculated.The steady absorption rate was calculated too by linear regression of cumulative release to time.Results The time to peak(tmax) of sinapine thiocyanate was 1.5 h,which was the maximum skin concentration appeared at 1.5 h after drug administration.The mean residence time(MRT) was about 22 h and the half time(t1/2) was about 15 h.The steady absorption rate was 13.65 μg/h.Conclusion Dermal pharmacokinetics of Baijiezi Tufang can be studied by microdialysis combined with RP-HPLC.And the dermal pharmacokinetics is in line with the characteristics of Baijiezi Tufang’s prevention and cure for asthma clinically.The combination of microdialysis with RP-HPLC is an appropriate study method.