title: Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and Disease: Part I: In Vitro Systems and Physiological Data.
abstract: The programme for the 2015 AAPS Annual Meeting and Exhibition (Orlando, FL; 25-29 October 2015) included a sunrise session presenting an overview of the state-of-the-art tools for in vitro-in vivo extrapolation (IVIVE) and mechanistic prediction of renal drug disposition. These concepts are based on approaches developed for prediction of hepatic clearance, with consideration of scaling factors physiologically relevant to kidney and the unique and complex structural organisation of this organ. Physiologically relevant kidney models require a number of parameters for mechanistic description of processes, supported by quantitative information on renal physiology (system parameters) and in vitro/in silico drug-related data. This review expands upon the themes raised during the session and highlights the importance of high quality in vitro drug data generated in appropriate experimental setup and robust system-related information for successful IVIVE of renal drug disposition. The different in vitro systems available for studying renal drug metabolism and transport are summarised and recent developments involving state-of-the-art technologies highlighted. Current gaps and uncertainties associated with system parameters related to human kidney for the development of physiologically based pharmacokinetic (PBPK) model and quantitative prediction of renal drug disposition, excretion, and/or metabolism are identified.
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scotcher
authors.affiliation: DMPK, Oncology iMed, AstraZeneca R&D Alderley Park, Macclesfield, Cheshire, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Jones
authors.affiliation: Drug Disposition, Lilly Research Laboratories, Indianapolis, Indiana, 46203, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Posada
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.|Simcyp Limited (a Certara Company), Blades Enterprise Centre, Sheffield, UK.
authors.forename: Amin
authors.initials: A
authors.lastname: Rostami-Hodjegan
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. Aleksandra.Galetin@manchester.ac.uk.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Galetin
mesh_terms: D000818:Animals; D003226:Congresses as Topic; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010829:Physiological Phenomena / Q000187:drug effects / Q000502:physiology*
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: active renal excretion; human kidney transporters; human renal drug clearance; kidney disease; non-hepatic drug metabolism