青蛾丸在更年期综合征患者中的暴露反应模型  

Exposure-response model of Qing-e pill in menopausal syndrome patients

作　　者：汪沉 郑青山[1] WANG Chen ZHENG Qingshan(Center for Drug Clinical Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203, China)

机构地区：[1]上海中医药大学药物临床研究中心,上海201203

出　　处：《中国临床药理学与治疗学》2017年第4期428-433,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：上海市进一步加快中医药事业发展三年行动计划(ZY3-CCCX-3-1001)

摘　　要：目的:建立青娥丸在更年期综合征患者体内的暴露-反应PK-PD模型,探讨植物雌激素对于女性更年期综合征的疗效以及个体因素对给药的影响。方法:基于青娥丸在更年期综合征患者临床试验数据,通过药物暴露-反应关系进行PKPD建模,并估算相关模型参数和变异。结果:最终选择药物中的有效成分补骨脂(其中含有14种香豆素类和黄酮类,总的有效成分含量占青娥丸总剂量的3.42%)作为体内的PK暴露量,PD指标采用24 h潮热次数相对基线的下降率。基础暴露反应模型为线性模型,模型参数Slope和Intercept的典型值(相对标准误%)分别为-56.2(10.2)和-14.6(22.2)。并添加体质量、疗程、剂量等因素作为模型的协变量。结论:对于青娥丸给药达12周以上,方能达到理想的疗效,而模拟不同体质量和给药疗程所建立的预测曲面模型提示,疗效和体质量呈负相关,与每日给药频次和疗程正相关。因此,针对不同患者根据体质量调节给药剂量,或疗效不佳者可适当加量、延长疗程。AIM： To develop an exposure-re- sponse PK-PD model of Qing-e pill in Chinese menopausal syndrome （MPS） patients so as to eval- uate 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 psorale- ae （ 14 coumarins and flavonoids with a total content of 3.42% of the whole Qing-er pill dosage） was se- lected as the PK exposure. The 24 h hot flashes de- creasing- 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 simu- lation 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.

关 键 词：青娥丸 更年期综合征 暴露-反应关系 药代动力学-药效动力学模型 

分 类 号：R969.1[医药卫生—药理学]