Paclitaxel Repackaged in an Albumin-Stabilized Nanoparticle: Handy or Just a Dandy? - Toxicity Limits

Paclitaxel Repackaged in an Albumin-Stabilized Nanoparticle: Handy or Just a Dandy?
Nov 2005
Alex Sparreboom, Sharyn D. Baker, and Jaap Verweij
Journal of Clinical Oncology
Clinical Pharmacology Research Core, National Cancer Institute, Bethesda, MD; The Department of Medical Oncology, Erasmus University Medical Center?Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
Pharmaceutical excipients have a vital role in drug formulations, a role that has tended to be neglected as evidenced by the lack of regulatory procedures to assess excipient safety outside a new drug application process.1 In contrast to earlier views, many of the currently used excipients are not inert vehicles, but can exert a range of intrinsic adverse effects and have the potential to cause clinically significant drug interactions. One of the best-studied excipients is polyoxyethylated castor oil (Cremophor El; Basf, Ludwigshafen, Germany), which is being used as a vehicle for the solubilization of a wide variety of hydrophobic drugs, including anesthetics, photosensitizers, sedatives, immunosuppressive agents, and anticancer drugs, such as teniposide and paclitaxel.2 The amount of Cremophor administered with such drugs averages 5 mL (range, 1.5-10 mL), although paclitaxel is an exception as the amount is much higher per administration, about 25 mL at the recommended dose of 175 mg/m2 once every three weeks. For this reason, there has been a surge of interest within both industry and academia in Cremophor's toxicological and pharmacologic profile in the context of chemotherapeutic treatment with paclitaxel.
Complete article is available online.