Newtaxel-A Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of action: Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The binding of docetaxel to microtubules does not alter the number of protofilaments.
Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for vital mitotic and interphase cellular functions.
Pharmacodynamic effects: Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular concentrations with a long cell residence time. In addition, docetaxel was found to be active on some but not all cell lines over expressing the p glycoprotein which is encoded by the multidrug resistance gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour activity against advanced murine and human grafted tumours.
Pharmacokinetics: Following intravenous administration, docetaxel is rapidly distributed to body tissues. It is extensively metabolized via hepatic cytochromes of the CYP3A4 group, and excreted chiefly in the faeces as metabolites. Only about 6% of a dose is excreted in urine within 7 days. The terminal elimination half-life is about 11 hours. Docetaxel is more than 95% bound to plasma proteins in the blood.