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Research on Pharmacokinetics and Analgesic Activity of Paeoniflorin and Glycyrrhizic Acid by Different Administration Routes

Author: YangYang
Tutor: WangQing；SunYuMing
School: Dalian University of Technology
Course: Pharmaceutical Engineering
Keywords: Paeoniflorin Glycyrrhizic acid Glycyrrhetinic acid Pharmacokinetics pharmacodynamics
CLC: R285
Type: Master's thesis
Year: 2011
Downloads: 216
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Abstract


Peony liquorice decoction was first recorded in Zhang Zhongjing’s Treatise on Febrile Diseases. It has been widely used to treat inflammation, pain, spasms, cough, asthma and ulcers and it also has an effect on uterine smooth muscle, gastrointestinal tract and two-ways regulation. Based on the study of peony liquorice decoction, its active components, paeoniflorin(PF) and glycyrrhizic acid(GL) was investigated. The pharmacokinetic interaction between PF and GL was explored, and the possible influence factors in this process was also investigated. Otherwise, PF-GA transdermal patch were prepared in this study, its permeation in vitro, local tissue distribution in vivo and analgesic activity were also studied.Compared with administrated with GL alone, Cmax and AUC of GL were decreased to 9% and 33%, respectively. Tmax was delayed significantly and CL was increased,distribution became wider; As for glycyrrhetinic acid, Tmax was delayed significantly and other parameters were no significant difference. GL also had an effect on the pharmacokinetics of PF in rats:Compared with PF using alone, Cmax and AUC were decreased significantly,and there was no significant change in peak time. It may be related with that PF was the substrate of P-gp, while, GL could regulate the level of P-gp.Effect of the concentration of GL in various tissue on the absorption of PF was explored in tissue distribution experiments. With the existing literature, it was found that the absorption of PF was associated with the concentration of GL in small intestine. After simultaneous administration of PF and GL,if the concentration of GL in small intestine was lower than 490μg/g,it would inhibit the absorption of PF,meanwhile,the inhibition was weaker as the increasing of the concentration of GL. It is favorable for the absorption of PF that GL was first administrated and then PF. The time interval was optimized, as the results, it is good for the absorption of PF when PF was given after the administration of GL.It was found that butyl alcohol was superior to propanediol to dissolve PF and GA during the preparation of PF-GA transdermal patch,and it was more conducive to the release of drug from the matrix. Different effects were appeared in various pressure-sensitive adhesives, the amount of release of PF and GL were higher in pressure-sensitive adhesive 87-4098, which was without functional group. The PF(15%)-GA(5%) trasdermal patch which were consist of butyl alcohol as solvent, IPM as penetration enhancer, pressure-sensitive adhesive 87-4098 as matrix, was with a 24h cumulative penetration amout of PF and GA,1187.30μg/cm2 and 817.49μg/cm2.As the result of local tissue distribution experiments of the patch, the concentration of PF and GA in the local tissue was in the order of the skin＞＞muscle> plasma. They were all reach the peak time at 8h in skin and muscle, the concentration of PF and GL were higher than that in blood. It was concluded that the drug might deep into the subcutaneous target tissue by a nearby topical application,and play its role in local treatment, and it also could pass through the skin into the blood capillaries for systemic action.The results of pharmacodynamic study showed that the PF-GA patch prepared in our study had an inhibitory effect on writhing induced by acetic acid,and had significantly lowered the writhing induced oxytocin in dysmenorrhea mice.PF-GA trasdermal patch was with a good inhibitory effect on inflammatory pain and spasm pain.

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