基于生理药动学模型计算氟甲喹在家兔体内的药动学参数

摘要

In order to illuminate the absorption ,distribution ,metabolism and excretion of flumequine in rabbits ,and to determine flumequine's optimal dosing regimen ,the physiological and anatomical parame-ters in rabbits were collected from the previous studies .Then a blood-flow limited physiologically based pharmacokinetics (PBPK) model including ten compartments was developed .The modules representing o-ral exposure ,gastrointestinal absorption ,and hepatic metabolism were incorporated into the present model to predict flumequine concentrations in tissues and plasma after one single oral dose at 15 mg/kg in rab-bits .The predicted plasma concentrations were subjected to compartmental and non-compartmental analy-ses to obtain the pharmacokinetics parameters of flumequine in rabbits .The results presented here showed that flumequine was rapidly absorbed ,extensively distrubuted into all tissues ,and eliminated rapidly from rabbits after oral administration .%为阐明氟甲喹（FL U ）在家兔体内的吸收、分布、代谢和排泄特点，为家兔疾病治疗中应用FL U提供合理的给药方案，通过文献检索获得了家兔的生理学和解剖学参数，之后建立了一个包含10个隔室在内的血流限速型生理药动学模型。模型中包含了FL U 的口服给药、胃肠道吸收及肝脏代谢模块。利用该模型成功模拟了家兔单次灌胃FLU（15 mg/kg）后各组织中的浓度，预测了FLU 的血浆浓度。通过对该血浆浓度-时间数据的进一步分析（房室分析和非房室分析），获得了灌胃给药后FL U 在家兔体内的药动学参数。结果表明，灌胃给药后，FL U在家兔体内吸收迅速，分布广泛，消除迅速。