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Paclitaxel
- indication:Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast.
- pharmacologypharmacology:
- mechanism: 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 β 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.
- toxicity: Rat (ipr) LD<sub>50</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.
- absorprion: I.V injected
- halflife: Average distribution half-life of 0.34 hours and an average elimination half-life of 5.8 hours.
- roouteelimination: In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
- volumedistribution: * 227 to 688 L/m2
- clearance: * 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h] * 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h] * 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h] * 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h]