Pharmacokinetics and pharmacodynamics of glycyrrhetinic acid with Paeoniflorin after transdermal administration in dysmenorrhea model mice

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• 作者：Xue Ding^a ; Yuming Sun^b ; Qing Wang ; ^a ; ^c ; ^{qwang@dlut.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Tingting Pu^a ; Xiaohui Li^d ; Yaqing Pan^a ; Yang Yang^a
• 关键词：Glycyrrhetinic acid ; Paeoniflorin ; Pharmacokinetics ; Pharmacodynamics ; Analgesic ; Transdermal drug delivery
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：23
• 期：8
• 页码：864-871
• 全文大小：1103 K

文摘

Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine.

Hypothesis/Purpose

The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics.

Study design and Methods

GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics.

Results and conclusion

In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48 h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy.