title: Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.
abstract: Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey, USA. xiaoyan_chu@merck.com
authors.forename: X
authors.initials: X
authors.lastname: Chu
authors.forename: K
authors.initials: K
authors.lastname: Korzekwa
authors.forename: R
authors.initials: R
authors.lastname: Elsby
authors.forename: K
authors.initials: K
authors.lastname: Fenner
authors.forename: A
authors.initials: A
authors.lastname: Galetin
authors.forename: Y
authors.initials: Y
authors.lastname: Lai
authors.forename: P
authors.initials: P
authors.lastname: Matsson
authors.forename: A
authors.initials: A
authors.lastname: Moss
authors.forename: S
authors.initials: S
authors.lastname: Nagar
authors.forename: G R
authors.initials: GR
authors.lastname: Rosania
authors.forename: J P F
authors.initials: JP
authors.lastname: Bai
authors.forename: J W
authors.initials: JW
authors.lastname: Polli
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: K L R
authors.initials: KL
authors.lastname: Brouwer
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D004347:Drug Interactions; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations