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Pharmacology: Pharmacodynamics: Docetaxel is a semisynthetic analogue of paclitaxel.
Systemic: Docetaxel is an antimitotic agent. It binds to free tubulin, then promotes the polymerization of tubulin into stable microtubules and inhibits microtubule disassembly, resulting in blockade of cellular mitotic and interphase functions and, consequently, in inhibition of cell division. Unlike paclitaxel and other spindle poisons in clinical use, docetaxel does not alter the number of protofilaments in the bound microtubules.
The mechanisms by which resistance to docetaxel occurs are not completely understood. Studies have shown that docetaxel is active against several tumor cell lines overexpressing the multidrug resistance gene. Also, cross-resistance between docetaxel and paclitaxel does not occur consistently. Several in vitro and in vivo studies have shown that docetaxel has only moderate immunosuppressive activity.
Pharmacokinetics: The kinetic profile of docetaxel is dose independent and consistent with a three-compartment pharmacokinetic model. The late phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment.
Distribution: Intravenous dosage docetaxel is rapidly distributed to body tissues. Docetaxel is more than 95% bound to plasma proteins.
Metabolism: It is extensively metabolized via hepatic cytochrome P450 isoenzyme CYP3A4.
Excretion: Docetaxel is excreted chiefly in the faeces as metabolites. Only about 6% of a dose is excreted in urine. The terminal elimination half-life is about 11 hours. Clearance is reduced in hepatic impairment.
