title: A novel matrix for the short-term storage of cells: utility in drug metabolism and drug transporter studies with rat, dog and human hepatocytes.
abstract: 1. The SureTran matrix is a novel method facilitating short-term maintenance of fresh primary hepatocyte cellular function and offers the potential use of primary cells "as fresh" for several days post isolation. In the study presented, the maintenance of several key phase I and II drug metabolizing enzyme and drug transporter activities is demonstrated with rat and dog hepatocytes preserved for up to 7 days after cell isolation. 2. Intrinsic clearance values were determined for 60 new chemical entities using rat hepatocytes freshly isolated at AstraZeneca and rat hepatocytes prepared at the facilities of Abcellute Ltd (SureTran purveyors), stored and incubated 24 hours after isolation. A very good correspondence in the intrinsic clearance values underlines the utility of the cell maintenance matrix. 3. For human hepatocytes many of the enzyme activities assayed were well maintained for 7 days of storage but some declined to below 50% of initial values between day 4 and 7 of storage. Human OATP1B1 activity was only determined with one batch and declined to 51% of the initial test value by day 4 and further down to 35% by day 7.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, AstraZeneca R&D Mölndal, Pepparedsleden, Sweden. anna-pia.palmgren@astrazeneca.com
authors.forename: Anna-Pia
authors.initials: AP
authors.lastname: Palmgren
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Fihn
authors.forename: James
authors.initials: J
authors.lastname: Bird
authors.forename: Paul
authors.initials: P
authors.lastname: Courtney
authors.forename: Ken
authors.initials: K
authors.lastname: Grime
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D001692:Biological Transport; D002469:Cell Separation; D015925:Cryopreservation / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D014453:Glucuronosyltransferase / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D006538:Heptanoic Acids / Q000378:metabolism; D006801:Humans; D027361:Organic Anion Transporters / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011758:Pyrroles / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity; D013535:Suspensions; D013997:Time Factors
chemical_list: D006538:Heptanoic Acids; D027361:Organic Anion Transporters; D004364:Pharmaceutical Preparations; D011758:Pyrroles; D013535:Suspensions; D003577:Cytochrome P-450 Enzyme System; D000069059:Atorvastatin; D014453:Glucuronosyltransferase