Pharmacokinetics and pharmacodynamics of glycyrrhetinic acid with Paeoniflorin after transdermal administration in dysmenorrhea model mice.
BACKGROUND
Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine.


OBJECTIVE
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.


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.


CONCLUSIONS
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 48h 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.
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.
Xue
X
Ding
Chemical Analysis and Research Center, Dalian University of Technology, Dalian, China.
Yuming
Y
Sun
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China. Electronic address: qwang@dlut.edu.cn.
Qing
Q
Wang
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.
Tingting
T
Pu
School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
Xiaohui
X
Li
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.
Yaqing
Y
Pan
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.
Yang
Y
Yang
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004412:Dysmenorrhea / Q000188:drug therapy*; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077239:Meloxicam; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012869:Skin Absorption; D013843:Thiazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D057968:Transdermal Patch; D006027:Glycosides
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D006034:Glycyrrhetinic Acid; D000077239:Meloxicam; D039821:Monoterpenes; D013843:Thiazines; D013844:Thiazoles; C015423:peoniflorin; D006027:Glycosides
Analgesic; Glycyrrhetinic acid; Paeoniflorin; Pharmacodynamics; Pharmacokinetics; Transdermal drug delivery