Coupled solutions of one- and two-compartment pharmacokinetic models with first-order absorption

This work emphasizes the importance of the fact, that plasma concentration profiles of one- and two-compartment linear pharmacokinetic (PK) models with first-order absorption introduce an uncertainty in data interpretation. PK-curve fitting results in a pair of valid solutions (coupled solutions), for which the derived PK parameters (such as AUC, MRT, Cmax, tmax, initial and terminal slope) are identical. Therefore, to make a proper choice of PK parameters of the drug in question, more information has to be considered, for example, which one of the solutions is more correlated with corresponding data, observed after iv administration. Comparison of different types of PK models and discussion on the transitions between the coupled solutions was carried out using a novel symbolic notation to provide more clarity and to simplify parameter indexing. Presented results were obtained by combined means of the method of statistic moments, Laplace transform and illustrated by the numerical experiment.