A multi-compartment pharmacokinetic model of docetaxel

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Kuhn, Alissa J.
University of Lethbridge. Faculty of Arts and Scince
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Lethbridge, Alta. : University of Lethbridge, Dept. of Physics and Astronomy
Docetaxel is a clinically active chemotherapeutic agent commonly used in the treatment of solid tumors. It is administered within a micelle encapsulation, polysorbate 80, via intravenous infusion. Docetaxel is known to have a high degree of interpatient variability in its pharmacokinetic behaviour. In this work, intensive, quantitative, compartmental pharmacokinetic models of docetaxel and its vehicle polysorbate 80 are developed. These models introduce both saturable kinetics and power-law relationships to the kinetic behaviour of these molecules. When fit to clinical data available in the literature by minimizing the weighted percentage variance these models out perform traditional linear models. A threecompartment model of docetaxel with both saturable and fractal effects is shown to accurately describe docetaxel pharmacokinetics. From this model pharmacokinetic metrics such as the maximum concentration, the area under the curve, and the half-life are derived. The sensitivity of this model’s parameters to interpatient variability is also investigated.
Pharmacokinetic , Interpatient variability , Chemotherapeutic agent , Docetaxel