Abstract:

AIM: To develop an exposure-response PK-PD model of Qing-e pill in Chinese menopausal syndrome (MPS)  patients so as to evaluate the efficiency of phytoestrogen and the effect of individual factors on administration.  METHODS: An exposure-response PK-PD model was established based on the clinical data of MPS patients. Related parameter and variability were thence estimated. RESULTS:The effective component-semen psoraleae (14 coumarins and flavonoids with a total content of 3.42% of the whole Qing-er pill dosage) was selected as the PK exposure. The 24 h hot flashes decreasing- rate from baseline was chosen as the PD indicator. The basic exposure-response model was a linear model. The typical values (RSE%) of model parameters (Slope and Intercept) were -56.2(10.2) and -14.6(22.2), respectively. Some other factors as body weight, course of treatment and dosage, etc. were included in the PK exposure part of the basic model. CONCLUSION: Treatment for at least 12 weeks is needed to achieve the ideal efficacy. A predicting surface model is built after simulation of different weights and courses, which indicate a negative correlation with weight but a positive correlation with drug frequency and treatment course. Therefore, specific dosage should be adjusted according to weight, and for patients presented with poor therapeutic effects, larger dose and longer course are suggested.

Key words: Qing-e pill, menopausal syndrome, E-R relationship, PK-PD model