Pharmacokinetics and anti-dysmenorrheal effect of paeonol polymorphs
Objective To determine the pharmacokinetic characteristics and difference in anti-dysmenorrhea effect of paeonol polymorphic forms(crystal forms Ⅰ～Ⅲ).Methods SD rats were orally administered with 3 crystal forms of paeonal at a dose of 138 mg·kg-1.The plasma concentrations of paeonal were determined with ultra-high-performance liquid chromatography.Estrogen and oxytocin were used to establish a rat model of primary dysmenorrhea(PD).The rats were orally administered with 3 crystal forms of paeonal at a dose of 138 mg·kg-1 repeatedly.Writhing latency and times of PD rats in each group were tested by behavioral assessment.ELISA kits were used to measure the levels of prostaglandin E2,nitric oxide,and tumor necrosis factor α in the uterine tissues,and HE staining was performed to evaluate histopathological changes in the uterine tissues.Results The main pharmacokinetic parameters of paeonal form Ⅰ,Ⅱ,and Ⅲ which were calculated by the non-compartment model as follows:Cmax was(0.98±0.23),(1.34±0.24),and(1.88±0.38)μg·mL-1;tmax was(120.00±0.00),(36.00±13.42),and(15.00±0.00)min;AUC0～7 h was(144.62±24.46),(97.64±24.14),and(104.32±20.25)min·μg·mL-1,t1/2 was(31.80±5.19),(27.57±4.24),and(28.34±4.74)min;and MRT0～7h was(126.74±6.86),(60.49±5.27),and(50.82±3.17)min.Paeonol had positive effect on PD rats,while different crystal forms resulted in different pharmacodynamic expressions.Crystal form Ⅰ had advantages in reducing the writhing times in the rats,improving the level of inflammatory factors and pathological changes in the uterus.Conclusion The dissolution and absorption rate of paeonal form Ⅰ are slower than those of other forms,which could better maintain the blood drug concentrations.Moreover,the anti-dysmenorrheal effect of form Ⅰ is also superior to other forms,indicating its promising potential in development and application.
万方数据
维普
