P-gp Inhibition-Based Strategies for Modulating Pharmacokinetics of Anticancer Drugs: An Update

E-ISSN： 1875-5453|17|8|806-826

ISSN： 1389-2002

Source： Current Drug Metabolism, Vol.17, Iss.8, 2016-08, pp. : 806-826

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Abstract

Background: P-glycoprotein (P-gp), a well known ATP dependent efflux membranetransporter, has been attracting considerable interests of medical researchers due to its effluxpump effect being a primary cause of multidrug resistance (MDR) and poor bioavailability (BA)of anticancer agents. How to resolve the aforesaid problems has become the research hot-pointsin the medical and pharmaceutical fields. The past three decades have witnessed rapid developmentof the P-gp inhibition-based strategies used for modulating pharmacokinetics (PK) and thusovercoming MDR and improving BA of anticancer drugs.Methods: An electronic search of PubMed database from inception to April, 2016 was conducted.Additionally, we searched the reference lists of included studies and carried out a citationsearch for the included studies via Web of Science to find other potentially relevant studies.Results and Conclusion: Lots of the studies of the P-gp inhibition-based strategies are underpreclinical phase and the obtained results are exciting and may represent great promise in theclinical application potential. In order to provide useful information for the development of novel strategies for improvingBA of anticancer drugs, this article aims to review the research progress in the P-gp inhibition-based strategiesthat has been acquired over the last three decades, with focus on the P-gp inhibitors, herbal constituents and pharmaceuticalexcipients as well as novel P-gp-linked drug delivery systems (DDSs). Additionally, the fundamental knowledgeon P-gp also is briefly discussed.