Structural Identifiability and Indistinguishability Analyses of in vitro Pitavastatin Hepatic Uptake

In this paper a review of the application of four different techniques (a version of the similarity transformation approach for autonomous uncontrolled systems, a non-differential input/output observable normal form approach, the characteristic set differential algebra and a recent algebraic input/output relationship approach) to determine the structural identifiability and indistinguishability of certain in vitro nonlinear pharmacokinetic models is provided. The Organic Anion Transporting Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear compartmental models have been derived to characterise the uptake process of Pitavastatin. As a prerequisite to parameter estimation, structural identifiability analyses are performed to establish that all unknown parameters can be identified from the experimental observations available. Furthermore, a structural indistinguishability analysis was performed to establish that all candidate models were structurally distinguishable for the given observations.This work is supported by the UK MRC Capacity Building Initiative and AstraZeneca.