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Paclitaxel volume of distribution

* 227 to 688 L/m^2 (apparent volume of distribution at steady-state, 24 hour infusion)

What is Paclitaxel

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. When it was developed commercially by Bristol-Myers Squibb (BMS), the generic name was changed to paclitaxel and the BMS compound is sold under the trademark Taxol. In this formulation, paclitaxel is dissolved in Kolliphor EL and ethanol, as a delivery agent. A newer formulation, in which paclitaxel is bound to albumin, is sold under the trademark Abraxane. (Wikipedia)

Paclitaxel mechanism of action

Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell’s ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the beta; subunit of tubulin. Tubulin is the “building block” of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.

Dosage forms of Paclitaxel

Indication of Paclitaxel

Used in the treatment of Kaposi’s sarcoma and cancer of the lung, ovarian, and breast. Abraxane is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.

Toxicity of Paclitaxel

Rat (ipr) LD sub50 /sub=32530 micro;g/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.