期刊
EXPERT OPINION ON DRUG DELIVERY
卷 11, 期 1, 页码 121-138出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425247.2014.865014
关键词
anticancer drugs; drug delivery system; P-glycoprotein; pharmacokinetics
Introduction: P-glycoprotein (P-gp) is a multi-specific efflux transporter belonging to ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, which significantly impacts the pharmacokinetics as well as multidrug resistance of anticancer drugs. Areas covered: This review explores how human P-gp transporters modulate the pharmacokinetics of anticancer drugs and emerging strategies to modulate their function. The key findings in direct modulation by various P-gp inhibitors on pharmacokinetics of various anticancer P-gp substrates are described. The role of pharmaceutical excipients as P-gp inhibitor with the focus on the recent development in novel drug delivery systems to modulate pharmacokinetics of anticancer drugs is also outlined. Expert opinion: The concomitant use of anticancer P-gp substrate and P-gp inhibitor is an effective and safe way to enhance the bioavailability of anticancer drugs. The poor bioavailability and toxicity of anticancer drugs limit their therapeutic efficacy. These characteristics can be improved by using various nanocarriers which exhibited a high potential to bypass this efflux protein. The best combination of P-gp inhibitor and substrate anticancer drug in a single nanocarrier formulation is a future challenge and is still probably some years away from the marketplace.
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