目的 比较雷公藤甲素（triptolide，TP）二元醇质体凝胶（binary ethosome gel，BEG）（TP@BEG）和TP普通凝胶（ordinary gel，OG）（TP@OG）皮肤药动学的行为差异，考察其在体经皮渗透性能。方法 采用体外增量法和体外减量法考察微透析探针体外回收率与传递率，同时建立了TP微透析方法，并通过微透析技术联合LC-MS/MS定量分析技术对TP的BEG和OG皮肤药动学进行了研究。结果 通过微透析数据整合发现，TP@OG和TP@BEG中TP皮下最大药物质量浓度（C_max）分别为185.12、116.13 ng/mL，半衰期（t_1/2）分别为3.35、3.10 h，达峰时间（t_max）分别为2.25、4.88 h，10 h内药时曲线下面积（AUC_0～10）分别为657.59、610.27 ng·h/mL。结论 TP@BEG在维持较高的生物利用度同时可延长药物在皮下组织中的滞留时间，具有更优的缓释作用，可望成为TP经皮给药的新剂型。

Objective To compare the pharmacokinetic behavior of triptolide (TP) binary ethosome gel (BEG) (TP@BEG) and TP ordinary gel (OG) (TP@OG), and to investigate the transdermal permeability of TP@BEG. Methods The in vitro recovery and transfer rate of TP microdialysis probe were investigated by in vitro increment method and in vitro dedosage method. TP microdialysis method was established, and the pharmacokinetics of TP@BEG and TP@OG skin were studied by microdialysis technique combined with LC-MS/MS quantitative analysis technique. Results Microdialysis data integration showed that the maximum subcutaneous drug concentration (C_max) of TP in TP@BEG and TP@OG were 185.12 ng/mL and 116.13 ng/mL, the half-life (t_1/2) were 3.35 h and 3.10 h, and the peak time (t_max) were 2.25 h and 4.88 h. The areas under the curve (AUC_0—10) were 657.59 ng·h/mL and 610.27 ng·h/mL, respectively.Conclusion TP@BEG can maintain high bioavailability and prolong the retention time in subcutaneous tissues, and has better sustained release effect. It is expected to be a new dosage form of TP for transdermal delivery.

R283.6

国家自然科学基金（82060722）；江西省自然科学基金（20202BAB206081）