期刊
INVESTIGATIONAL NEW DRUGS
卷 19, 期 2, 页码 125-141出版社
SPRINGER
DOI: 10.1023/A:1010618632738
关键词
Cremophor EL; paclitaxel; Tween 80; docetaxel; pharmacokinetics
The non-ionic surfactants Cremophor EL (CrEL) and Tween 80, both used as formulation vehicles of many (anticancer) agents including paclitaxel and docetaxel, are not physiological inert compounds. We describe their biological properties, especially the toxic side effects, and their pharmacological properties, such as modulation of P-glycoprotein activity. In detail, we discuss their influence on the disposition of the solubilized drugs, with focus on CrEL and paclitaxel, and of concomitantly administered drugs. The ability of the surfactants to form micelles in aqueous solution as well as biological fluids (e.g. plasma) appears to be of great importance with respect to the pharmacokinetic behavior of the formulated drugs. Due to drug entrapment in the micelles, plasma concentrations and clearance of free drug change significant leading to alteration in pharmacodynamic characteristics. We conclude with some perspectives related to further investigation and development of alternative methods of administration.
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