PITFALLS IN PHARMACOKINETIC MULTICOMPARTMENT ANALYSIS

When a pharmacokinetic (PK) two-compartment body model with first-orde r absorption is fitted to blood levels of a drug, the estimates of the PK parameters may have considerable errors and can cause wrong predic tions in other features of the system. The objectives of this report w ere to illustrate this problem, to provide an easy way to prevent wron g estimation, and to investigate the origin of the mistake. A simple w ay to prevent wrong interpretation of the calculated PK parameters is to inspect the PK profiles visually. Without observing a clear biphasi c profile, one should not apply the two-compartment model if the resul ting parameters are to be interpreted and used for further simulations . We investigated the origin of this ambiguity in terms of the relativ e order of magnitude of microconstants (k(a), k(12), k(21), and k(10)) and of hybrid constants (A and B). The observed parameter errors will not be of any relevance if the calculated parameters are used only to predict future blood levels over the same time-span. However, if thes e parameters are used to predict any other characteristic of the syste m, erroneous predictions may result.