抗肿瘤药物多柔比星的PBPK模型研究进展

A review on the physiologically based pharmacokinetic(PBPK)of doxorubicin

多柔比星(doxorubicin,DOX)在临床广泛应用于实体肿瘤、淋巴瘤和白血病等的治疗。DOX的细胞毒性作用和心脏毒性作用,使得其在发挥抗肿瘤作用的同时也产生严重毒副作用,限制了临床应用。这促使研究者不断深入了解其体内药动学、作用机制,找到适宜的临床治疗方案,以及开发出新的制剂或给药系统。在DOX的研究过程中,基于生理的药物动力学模型(physiologically based pharmacokinetic model,PBPK)发挥了非常重要的作用。本文从DOX的PBPK模型发展到应用于DOX给药方案设计、药动学影响因素分析、细胞毒性和心脏毒性作用机制以及指导DOX前药及新制剂开发研究等方面进行介绍,对DOX的PBPK模型发展及其应用进展进行了概述。

Doxorubicin(DOX)has been widely used in the treatment of solid tumors,lymphoma and leukemia.The cytotoxic and cardiotoxic effects of DOX make it produce serious toxic side effects while exerting anti-tumor effects,which limits its clinical application.This has led to a continuous understanding of their in vivo pharmacokinetics,mechanism of action,idenfication of appropriate clinical treatment options,and the development of new formulations or drug delivery systems.During the study of DOX,physiologically based pharmacokinetic model(PBPK)plays a very important role.In this paper,the development of DOX PBPK model to the application of DOX dosing regimen design,pharmacokinetic factors analysis,cytotoxicity and cardiotoxicity mechanism of action and guide the development of DOX prodrugs and new preparations are introduced,and the development and application progress of DOX PBPK model are summarized.