title: The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance.
abstract: Over the last two decades the impact on drug pharmacokinetics of the organic anion transporting polypeptides (OATPs: OATP-1B1, 1B3 and 2B1), expressed on the sinusoidal membrane of the hepatocyte, has been increasingly recognized.        OATP-mediated uptake into the hepatocyte coupled with subsequent excretion into bile via efflux proteins, such as MRP2, is often referred to as hepatobiliary excretion.        OATP transporter proteins can impact some drugs in several ways including pharmacokinetic variability, pharmacodynamic response and drug-drug interactions (DDIs).        The impact of transporter mediated hepatic clearance is illustrated with case examples, from the literature and also from the Pfizer portfolio.        The currently available in vitro techniques to study the hepatic transporter proteins involved in the hepatobiliary clearance of drugs are reviewed herein along with recent advances in using these in vitro data to predict the human clearance of compounds recognized by hepatic uptake transporters.
authors.affiliation: Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Sandwich, Kent, UK. katherine.fenner@astrazeneca.com
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Fenner
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jones
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ullah
authors.forename: Sarah
authors.initials: S
authors.lastname: Kempshall
authors.forename: Maurice
authors.initials: M
authors.lastname: Dickins
authors.forename: Yurong
authors.initials: Y
authors.lastname: Lai
authors.forename: Paul
authors.initials: P
authors.lastname: Morgan
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Barton
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000493:pharmacokinetics; D057911:Angiotensin Receptor Antagonists / Q000493:pharmacokinetics; D001659:Biliary Tract / Q000201:enzymology / Q000378:metabolism*; D004347:Drug Interactions; D004335:Drug and Narcotic Control; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D013045:Species Specificity
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D057911:Angiotensin Receptor Antagonists; D006634:Histamine H1 Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027361:Organic Anion Transporters; D004364:Pharmaceutical Preparations