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By John R. Krueger

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Lumped Deterministic Models Often a lumped parameter representation is adequate for describing the dynamics of a metabolic system . This implies that distributed effects are lumped together and treated as a homogeneous entity. For instance, reference to the plasma concentration of a metabolite implies a lumped representation, with concentration gradients in the plasma being disregarded and homogeneity assumed. Mathematically, the aggregation involved in a lumped representation leads to ordinary differential equations, as opposed to the partial differential equations which would be required to describe distributed effects.

We have never had this awful experience. MAJOR FEATURES OFSEQUENTIALLY OPTIMISED EXPERIMENTS Results to date have been surprisingly consistent and very encouraging. They have provided us with a sharpened intuition about kinetic experiment design, a number of useful rules of thumb and cost-savingfeatures for the experimental laboratory, and some stimulating ideas for further research. Some major results are listed below. , reference 10). This was not a result of near-optimality of the prior model, because some parameter estimates were significantly different in the final model, and parameter coefficients of variation (CV) were reduced more than 30 per cent on the average.

For kinetic studies in biological systems, given these kinds of relatively problematic methodological limitations, simple multicompartmental models, with 1-4 pools'', and so-called non-compartmental models' are typical of the representations in common usage. And each of these has its own problems, proponents and opponents'v", Consequently, at the whole organism level, particularly in human plasma protein studies where blood and urine are usually 16 J. J. DiStefano, III the only feasible output measurement ports and intravenous injection is usually the only reasonable test input route, only a handful of useful kinetic parameters can be obtained from such models.

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