Optimization issues in physiological toxicokinetic modeling: a case study with benzene
1993; Elsevier BV; Volume: 69; Issue: 2 Linguagem: Inglês
10.1016/0378-4274(93)90103-5
ISSN1879-3169
AutoresTracey J. Woodruff, Frédéric Y. Bois,
Tópico(s)Computational Drug Discovery Methods
ResumoThis paper compares two methods for global optimization of physiologically based toxicokinetic models: Monte Carlo optimization, which searches randomly for the optimum; and the simplex method, which updates systematically an array of parameter values. Two measures of goodness-of-fit are also contrasted: criterion function and likelihood. A 14-parameter model of benzene distribution in rats is used to illustrate these 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.
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