基于生理药物代谢动力学模型预测氯氮平联合用药的药物相互作用

牟凡, 黄志伟, 程渝, 赵雪, 李华芳, 禹顺英

Prediction of drug-drug interactions in clozapine combination therapy based on physiologically based pharmacokinetic model

MOU Fan, HUANG Zhiwei, CHENG Yu, ZHAO Xue, LI Huafang, YU Shunying

表2 氯氮平和氟伏沙明的基本理化性质及ADME相关参数

Tab 2 Basic physicochemical properties and ADME-related parameters of clozapine and fluvoxamine

Parameter Clozapine Source Fluvoxamine Source LogP 3.23 DrugBank 3.68 Fitted fu 0.02 FDA, fitted 0.20 DrugBank, fitted Molecular weight/(g·mol-1) 326.83 DrugBank 318.34 DrugBank pKa 7.50 DrugBank 9.40 Fitted Solubility/(mg·mL-1) 0.19 ALOGPS 0.07 Fitted CLh/(mL·h-1·kg-1) 2.28 Fitted 1.21 Fitted CLr/(mL·h-1·kg-1) 0.01 Fitted 0.02 FDA, fitted