Claxel Mechanism of Action

Pharmacology: Pharmacodynamics: Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular function. In addition, paclitaxel induces abnormal arrays or bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Pharmacokinetics: Following intravenous administration, paclitaxel exhibits a biphasic decline in plasma concentrations.
The pharmacokinetics of paclitaxel was determined following 3 and 24 hour infusions at doses of 135 and 175 mg/m². Mean terminal half-life estimates ranged from 3.0 to 52.7 hours, and mean, non-compartmentally derived, values for total body clearance ranged from 11.6 to 24.0 l/hr/m²; total body clearance appeared to decrease with higher plasma concentrations of paclitaxel. Mean steady-state volume of distribution ranged from 198 to 688 l/m², indicating extensive extravascular distribution and/or tissue binding. With the 3-hour infusion, increasing doses result in non-linear pharmacokinetics. For the 30% increase in dose from 135 mg/m² to 175 mg/m², the Cmax and AUC→∞ values increased 75% and 81%, respectively.
Following an intravenous dose of 100 mg/ m² given as a 3-hour infusion to19 KS patients, the mean Cmax was 1,530 ng/ml (range 761 - 2,860 ng/ml) and the mean AUC 5,619 ng·h/ml (range 2,609- 9,428 ng·hr/ml). Clearance was 20.6 l/h/m² (range 11-38) and the volume of distribution was 291 l/m² (range 121- 638). The terminal elimination half-life averaged 23.7 hours (range 12 - 33).