Stochastic vs. deterministic uptake of dodecanedioic acid by isolated rat livers

• Published in: Bulletin of mathematical biology 2005-05, Vol.67 (3), p.547-561
• Main Authors: Ditlevsen, Susanne, de Gaetano, Andrea
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Chromatography, High Pressure Liquid; Dicarboxylic Acids - metabolism; Dicarboxylic Acids - pharmacokinetics; In Vitro Techniques; Least-Squares Analysis; Likelihood Functions; Liver - metabolism; Male; Models, Biological; Models, Statistical; Monte Carlo Method; Parameter estimation; Perfusion; Rats; Rats, Wistar; Stochastic Processes; Studies
• ISSN: 0092-8240; 1522-9602
• DOI: 10.1016/j.bulm.2004.09.005

Deterministic and stochastic differential equations models of the uptake of dodecanedioic acid (C12) are fitted to experimental data obtained on nine isolated, perfused rat livers. 11500 μg of C12 were injected as a bolus into the perfusing liver solution. The concentrations of C12 in perfusate samples taken over 2 h from the beginning of the experiments were analyzed by High Performance Liquid Chromatography (HPLC). A two-compartment deterministic model is studied. To include spontaneous erratic variations in the metabolic processes the parameter for the uptake rate is randomized to obtain a stochastic differential equations model. Parameters are estimated in a two-step procedure: first, parameters in the drift part are estimated by least squares; then, the diffusion parameter is estimated using Monte-Carlo simulations to approximate the unknown likelihood function. Parameter estimation is carried out over a wide range of reasonable measurement error variances to check robustness of estimates. It is concluded that the kinetics of dodecanedioic acid, in the experimental conditions discussed, is well approximated by a model including spontaneous erratic variations in the liver uptake rate.