The problem of model indistinguishability in pharmacokinetics

The problem of model indistinguishability is introduced in the context of linear compartmental models in pharmacokinetics. The two most widely used methods of analyzing model indistinguishability are described. It is shown that as the number of compartments increases, one approach, based on the Laplace transforms of the observations, although conceptually simple, can result in very large numbers of candidate models to be examined for indistinguishability, while the other approach, based on similarity transformations, although systematic, often results in very difficult algebraic expressions. These problems can be eased by the use of some simple geometrical rules, used at the outset of an indistinguishability analysis. The approach is illustrated by application of two 2-compartment drug, 2-compartment metabolite models.