目的 建立丹参酮II_A（tanshinone II_A，TSA）微透析取样方法，探究TSA微针皮肤药动学特征。方法 建立TSA分析方法，确定内标物吉非罗齐（gemfibrozil，GEM）分析方法的可行性。采用增量法和减量法，考察TSA回收率、GEM释放率以及P值稳定性，建立体外微透析取样系统。兔耳经皮给予丹参酮II_A微针，GEM作为微透析采样的内标物，测定TSA皮肤药物浓度，采用DSA 2.0软件对药动学数据进行处理，绘制药物浓度-时间曲线。结果 药物回收率与灌流体积流量呈反比，与温度呈正比，不受探针外液浓度的影响，P值可保持良好稳定性。GEM对TSA无干扰，P值在体校正后均值为（60.04±1.90）%。在TSA微针的药动学参数和药时曲线中，TSA微针组的药物浓度明显高于TSA药液组，且曲线平缓，药物平均滞留时间（MRT_0→12）为（5.1±1.3）h。结论TSA微针给药后，皮肤组织中浓度较为稳定，有明显的缓释效果。

ObjectiveTo establish the tanshinone Ⅱ_A (TSA) microdialysis sampling method and explore the skin pharmacokinetic characteristics of TSA microneedles. Methods A TSA analysis method was established to determine the feasibility of internal standard gemfibrozil (GEM) analysis method. The incremental method and decrement method were used to investigate TSA recovery rate, GEM release rate and stability of P value, and an in vitro microdialysis sampling system was established. TSA microneedle was administered transdermally to rabbit ears, GEM was used as internal standard for microdialysis sampling to determine the TSA skin drug concentration. DSA 2.0 software was used to process the pharmacokinetic data and draw the drug concentration-time curve. Results The recovery rate of drug was inversely proportional to perfusion speed, and was positively proportional to temperature without being affected by the concentration of outer liquid of probe, and P value could maintain a good stability. GEM had no interference to TSA, and the average P value after body correction was (60.04 ±1.90) %. In pharmacokinetic parameters and drug-time curve of TSA microneedle, the drug concentration of TSA microneedle group was significantly higher than that of TSA liquid group, and the curve was flat. The average drug retention time (MRT_0→12) was (5.1 ±1.3) h. Conclusion After TSA microneedles is administered, the concentration in skin tissue is relatively stable and has obvious sustained-release effect.

R285.61

国家自然科学基金资助项目（82173982）；广东省高等学校优秀青年教师培养计划项目（YQ2015099）