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Abstract
Taxanes, including paclitaxel and docetaxel, are widely used cytotoxic agents for the treatment of solid tumors. Paclitaxel, a small, hydrophobic agent, binds extensively to plasma proteins, and its pharmacokinetic profile is characterized by a short plasma elimination half-life with a broad tissue distribution. These unfavorable pharmacokinetic characteristics are associated with limited tumor exposure and high systemic exposure, reducing the therapeutic index of paclitaxel. Paclitaxel poliglumex (PPX, CT-2103), a polymer–drug conjugate of paclitaxel and poly-L-glutamic acid, was designed to enhance the therapeutic index of paclitaxel by improving its pharmacokinetic profile, and to provide a water-soluble alternative to the standard paclitaxel formulation. Potential advantages of polymer–drug conjugates include delivery of a higher concentration of active drug to tumor tissue and limited exposure of normal tissues. In addition, the slow release of drug from the polymer carrier lowers peak plasma concentrations of the active drug.
Disclosure
Philip Bonomi has received consultant honoraria and research support from CTI.
