The Incorporation of Fractal Kinetics in the PK Modeling of Chemotherapeutic Drugs with Nonlinear Concentration-Time Profiles

Paclitaxel is a well-known chemotherapeutic drug which has been successfully used in the treatment of various cancers. Clinical studies confirm that the concentration-time profile of this very important drug is nonlinear. In order to capture this non-linearity, various multi-compartmental models with both saturable distribution and elimination (usually under the assumption that various PK processes are governed by Michaelis–Menten kinetics) have been developed and published in the literature. These models have been successful (to some degree), even though it has been observed that complex biological systems are often heterogeneous media displaying fractal geometry. Furthermore, the assumption of classical Michaelis–Menten kinetics could be a shortcoming when attempting to capture the nonlinear behavior of many drugs. In this paper, we propose a two compartmental model, incorporating steady state, fractal Michaelis–Menten Kinetics. The model is an extension of an existing model that uses classical Michaelis–Menten kinetics. However, comparison of both models suggests that our model is better able to capture the nonlinear behavior of paclitaxel.