作　　者： (章袁）; (朱立勤）; (亓芳）; (周秀杰）;

机构地区： 天津市第一中心医院,天津300192

出　　处： 《中国新药杂志》 2017年第17期2097-2100,共4页

摘　　要： 目的:建立伏立康唑(voriconazole)与奥美拉唑(omeprazole)间药物相互作用(drug-drug interactions,DDIs)模型,探讨两者合用的药动学过程,为临床合理用药提供理论参考。方法:通过文献检索和收集伏立康唑与奥美拉唑的理化性质参数、体外酶促动力学参数等数据,建立生理药动学(physiologically based pharmacokinetic,PBPK)模型,模型验证后再建立两者的DDIs模型,预测两者合用时药动学过程的变化。结果:当两者合用时,奥美拉唑会使体内伏立康唑的最大血药浓度(C_(max))、血药浓度-时间曲线下总面积(AUC_(0-inf))和截止至终末观察点时的血浆药物浓度-时间曲线下面积(AUC_(0-t))增加,增加的比率分别为16.5%,38.7%和37.5%。结论:当伏立康唑与奥美拉唑合用时,奥美拉唑会增加体内伏立康唑的血药浓度,但增加的伏立康唑血药浓度仍在其治疗窗之内。因此,临床上2种药物合用时,无需调整伏立康唑的给药剂量。 Objective： To establish the drug-drug interactions model between voriconazole and omeprazole and explore the influence of the pharmacokinetics when co-administered with each other,and to provide theoretical reference for the rational use of drugs in the clinical practices. Methods： The physicochemical properties parameter,in vitro parameters and pharmacokinetic data of voriconazole and omeprazole were retrieved and collected. The PBPK model of voriconazole and omeprazole was respectively established and verified. Finally,the drug-drug interactions model was established on the basis of these models. Results： The drug-drug interactions model showed that omeprazole will affect the voriconazole plasma concentration,the maximum plasma concentration（ C（max））,total area under the plasma concentration time curve（ AUC（0-inf）） of voriconazole and area under the plasma concentration time curve of voriconazole at the end of the observation point（ AUC（0-t）） were increased. The increase rates were 16. 5%,38. 7% and 37. 5%,respectively. Conclusion： This study showed that omeprazole can increase voriconazole plasma concentration when co-administered with voriconazole. Due to the increased blood plasma concentration of voriconazole was within the therapeutic window,the doseage adjusting of voriconazole was unnecessary when co-administered with omeprazole.

关 键 词： 伏立康唑 奥美拉唑 生理药动学模型 药物相互作用模型