OPTIMIZATION ISSUES IN PHYSIOLOGICAL TOXICOKINETIC MODELING - A CASE-STUDY WITH BENZENE

This paper compares two methods for global optimization of physiologic ally based toxicokinetic models: Monte Carlo optimization, which searc hes randomly for the optimum; and the simplex method, which updates sy stematically an array of parameter values. Two measures of goodness-of -fit are also contrasted: criterion function and likelihood. A 14-para meter model of benzene distribution in rats is used to illustrate thes e techniques. Simplex optimization yields better fits overall. However , the measurement of uncertainty offered by Monte Carlo simulations is a major argument in favor of their use.