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Role of Formulation Vehicles in Taxane Pharmacology

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Abstract

The non-ionic surfactants Cremophor EL (CrEL) and Tween 80,both used as formulation vehicles of many (anticancer) agentsincluding paclitaxel and docetaxel, are not physiologicalinert compounds. We describe their biological properties,especially the toxic side effects, and their pharmacologicalproperties, such as modulation of P-glycoprotein activity. Indetail, we discuss their influence on the disposition of thesolubilized drugs, with focus on CrEL and paclitaxel, and ofconcomitantly administered drugs. The ability of thesurfactants to form micelles in aqueous solution as well asbiological fluids (e.g. plasma) appears to be of greatimportance with respect to the pharmacokinetic behavior of theformulated drugs. Due to drug entrapment in the micelles,plasma concentrations and clearance of free drug changesignificant leading to alteration in pharmacodynamiccharacteristics. We conclude with some perspectives related tofurther investigation and development of alternative methodsof administration.

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  1. Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), University Hospital Rotterdam, Rotterdam, The Netherlands

    Lia van Zuylen, Jaap Verweij & Alex Sparreboom

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van Zuylen, L., Verweij, J. & Sparreboom, A. Role of Formulation Vehicles in Taxane Pharmacology. Invest New Drugs 19, 125–141 (2001). https://doi.org/10.1023/A:1010618632738

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