title: ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans.
abstract: This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational interpretation of transporter-knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter-mediated pharmacokinetics and drug-drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science.
authors.affiliation: Drug Disposition, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Zamek-Gliszczynski
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Poirier
authors.forename: J
authors.initials: J
authors.lastname: Bentz
authors.forename: X
authors.initials: X
authors.lastname: Chu
authors.forename: H
authors.initials: H
authors.lastname: Ellens
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Jamei
authors.forename: J C
authors.initials: JC
authors.lastname: Kalvass
authors.forename: S
authors.initials: S
authors.lastname: Nagar
authors.forename: K S
authors.initials: KS
authors.lastname: Pang
authors.forename: K
authors.initials: K
authors.lastname: Korzekwa
authors.forename: P W
authors.initials: PW
authors.lastname: Swaan
authors.forename: M E
authors.initials: ME
authors.lastname: Taub
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Galetin
mesh_terms: D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004347:Drug Interactions; D017408:Guidelines as Topic; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations