Nonlinear pharmacokinetics of tissue-type plasminogen activator in three animal species: a comparison of mathematical models

A recent study presented plasma concentrations of tissue-type plasminogen activator in three different animal species and at several different dose levels. A three-compartment mammillary model with capacity-limited elimination (of Michaelis-Menten form) was postulated to describe the data. In the present study, several alternative model structures are examined with the view of determining whether better fits can be obtained, whether linear models are significantly worse than nonlinear models, and whether all three compartments are really necessary.