摘要
目的研究隐丹参酮皮肤角质类脂体的药效学与其有效成分隐丹参酮的药动学,探讨其药动学与药效学的相关性。方法采用微透析采样法对痤疮大鼠局部组织液进行采样,并用高效液相色谱法测定隐丹参酮的含量;用液相芯片法检测药效学指标IL-1α和AR的含量,以效应-时间-药物浓度绘制曲线并进行相关分析;采用DAS软件对药物效应-血药浓度进行药物代谢动力学与药物效应动力学(PK-PD)模型拟合。结果隐丹参酮皮肤角质类脂体凝胶皮肤局部给药后2 h药物浓度达到峰值,药效动力学指标IL-1α和AR的含量最小值分别出现在大约6 h和4 h,说明药物浓度与药效之间具有一定的滞后性。药效动力学指标IL-1α和AR与隐丹参酮浓度之间的关系符合效应抑制模型。结论初步研究表明,隐丹参酮皮肤角质类脂体凝胶的局部药动学与局部药效学具有一定的相关性。
Objective The drug concentration and efficacy of cryptotanshinone cerasomes gel in topical acne skin were studied in order to investigate the preliminary correlation of pharmacokinetics and pharmacodynamics(PK-PD).Methods Using microdialysis sampling technique,we obtained the intradermal fluid samples for detecting concentration of cryptotanshinone by HPLC and contents of IL-1αand AR by luminex method.PK-PD modeling was adopted by analysis of the effect-time-drug concentration curve using DAS software.Results The peak concentration of cryptotanshinone was shown at about 2 h and the minimum concentration of pharmacodynamics index IL-1αand AR appeared at about 6 h and 4 h,showing a certain lag effect.And the relationship of effect and concentration of IL-1αand AR were accorded with the effect inhibition model.ConclusionPreliminary studies indicated that pharmacodynamics of cryptotanshinone cerasomes gel and pharmacokinetics of its main component cryptotanshinone are relevant.
引文
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