title: Structural identifiability analyses of candidate models for in vitro Pitavastatin hepatic uptake.
abstract: 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 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.
authors.affiliation: School of Engineering, University of Warwick, Coventry CV4 7AL, UK. Electronic address: t.grandjean@warwick.ac.uk.
authors.forename: Thomas R B
authors.initials: TR
authors.lastname: Grandjean
authors.affiliation: School of Engineering, University of Warwick, Coventry CV4 7AL, UK. Electronic address: M.J.Chappell@Warwick.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chappell
authors.affiliation: AstraZeneca R&D, Alderley Park, Macclesfield SK10 4TG, UK. Electronic address: James.Yates@AstraZeneca.com.
authors.forename: James W T
authors.initials: JW
authors.lastname: Yates
authors.affiliation: School of Engineering, University of Warwick, Coventry CV4 7AL, UK. Electronic address: Neil.Evans@warwick.ac.uk.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Evans
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects*; D008954:Models, Biological; D011804:Quinolines / Q000493:pharmacokinetics*; D012984:Software
chemical_list: D011804:Quinolines; C108475:pitavastatin
keywords: Compartmental models; Pitavastatin; Structural identifiability