Open AccessA model of competing saturable kinetic processes with application to the pharmacokinetics of the anticancer drug paclitaxel
Author(s) -
Rebeccah E. Marsh,
Jack A. Tuszyński,
Michael B. Sawyer,
K. J. E. Vos
Publication year - 2011
Publication title -
mathematical biosciences and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 45
eISSN - 1551-0018
pISSN - 1547-1063
DOI - 10.3934/mbe.2011.8.325
Subject(s) - pharmacokinetics , exponent , power law , paclitaxel , statistical physics , crossover , distribution (mathematics) , compartment (ship) , mathematics , chemistry , law , physics , pharmacology , computer science , cancer , medicine , statistics , mathematical analysis , philosophy , linguistics , oceanography , artificial intelligence , political science , geology
A saturable multi-compartment pharmacokinetic model for the anti-cancer drug paclitaxel is proposed based on a meta-analysis of pharmacokinetic data published over the last two decades. We present and classify the results of time series for the drug concentration in the body to uncover the underlying power laws. Two dominant fractional power law exponents were found to characterize the tails of paclitaxel concentration-time curves. Short infusion times led to a power exponent of -1.57 ± 0.14, while long infusion times resulted in tails with roughly twice the exponent. Curves following intermediate infusion times were characterized by two power laws. An initial segment with the larger slope was followed by a long-time tail characterized by the smaller exponent. The area under the curve and the maximum concentration exhibited a power law dependence on dose, both with compatible fractional power exponents. Computer simulations using the proposed model revealed that a two-compartment model with both saturable distribution and elimination can reproduce both the single and crossover power laws. Also, the nonlinear dose-dependence is correlated with the empirical power law tails. The longer the infusion time the better the drug delivery to the tumor compartment is a clinical recommendation we propose.