and dispositionDrug Metabolism

and dispositionDrug Metabolism

A Publication of the American Society for Pharmacology and Experimental Therapeutics

Volume 36 ■ Number 1 ■ January 2008 ■ ISSN 0090-9556

zdd0010800SPC1.qxd 12/14/07 8:43 AM Page 1

DRUG METABOLISM AND DISPOSITIONA Publication of the American Society for Pharmacology and Experimental Therapeutics

Founded by Kenneth C. Leibman—1973

Eric F. Johnson, Editor

ASSOCIATE EDITORSStephen D. Hall, Laurence S. Kaminsky, Russell A. Prough, John D. Schuetz, Jeffrey C. Stevens,

Kenneth E. Thummel, Donald J. Tweedie, Steven A. Wrighton, and Garold S. Yost

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Ronald B. FranklinG. Gordon GibsonJoyce GoldsteinRobert HanzlikRonald N. HinesPaul F. HollenbergJ. Brian HoustonMagnus Ingelman-

SundbergPhilip B. InskeepMargaret O. JamesJeffrey P. Jones

Richard KimSang Geon KimThomas KocarekDennis R. KoopLawrence H. LashJ. Steven LeederLois D. Lehman-

McKeemanPeter Ian MackenzieEdward T. MorganSidney D. NelsonR. Scott Obach

K. Sandy PangAnna Radominska-

PandyaJudy L. RaucyAllan RettieDouglas RickertDavid S. RiddickJoseph K. RitterA. David RodriguesMelissa Runge-MorrisMagang ShouBill J. Smith

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ASPET EXECUTIVE OFFICER: Christine K. CarricoJournals Director: Richard Dodenhoff Managing Editor: Jill Filler Senior Editorial Coordinator: Rhonda Frankenfield

Journal and ASPET Office: 9650 Rockville Pike, Bethesda, MD 20814-3995; telephone: 301-634-7060; fax: 301-634-7061; email: info@aspet.org;web site: www.aspet.org.Correspondence regarding editorial matters should be addressed to Dr.Eric F. Johnson, Editor, Drug Metabolism and Disposition, at the aboveaddress.Official version: The online version of Drug Metabolism and Dispositioncontains all of the information and material contained in the print version plusadditional material that may not appear in print such as videos and large datasets. The online version may be more current than the print version. Wherenoted, the online version has been corrected in departure from the printversion. The online version of Drug Metabolism and Disposition officiallypublished by the American Society for Pharmacology and ExperimentalTherapeutics is the definitive version and, to the extent any difference exists,will prevail over the print version.Instructions to Authors: See http://dmd.aspetjournals.org for the Instruc-tions to Authors and the ASPET Authorship Responsibility, Financial Dis-closure, and Copyright Transfer form.Correspondence concerning subscriptions: Nonmember individual and in-stitutional subscriptions: ASPET Subscriptions Dept., Rm. L-2310, 9650Rockville Pike, Bethesda, MD 20814-3998; telephone: 301-634-7029; fax:301-634-7099; email: staff@dues.faseb.org. ASPET Members: contact theASPET office. For European site licenses and consortia, contact: DavidCharles, Institutional Sales & Licensing, 92 avenue du General de Gaulle,78600 Maisons-Laffitte, France: telephone: �33–1-39–12-29–29; fax: �33–1-39–12-47–45; email: dlcharles@wanadoo.fr.Change of address: ASPET must be notified 60 days in advance. Journalsundeliverable because of incorrect address will be destroyed. Duplicate copiesmay be obtained, if available, from ASPET at the single copy price. Sendaddress changes to the ASPET office.Issue Replacement Policy: Domestic Subscribers—Claims for nondelivery

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January 2008 Vol. 36, No. 1

CONTENTS

MINIREVIEW

The Development of Drug Metabolism Research asExpressed in the Publications of ASPET: Part 1,1909–1958. Patrick J. Murphy . . . . . . . . . . . . 1

SHORT COMMUNICATIONS

Oseltamivir (Tamiflu) Efflux Transport at the Blood-Brain Barrier via P-Glycoprotein. Kaori Morimoto,Masanori Nakakariya, Yoshiyuki Shirasaka, Chi-haya Kakinuma, Takuya Fujita, Ikumi Tamai,and Takuo Ogihara . . . . . . . . . . . . . . . . . . . 6

The Effects of ABCB1 3�-Untranslated Region Vari-ants on mRNA Stability. Jason M. Gow, LeslieW. Chinn, and Deanna L. Kroetz . . . . . . . . . . 10

ARTICLES

Gender Differences in mRNA Expression of ATP-Binding Cassette Efflux and Bile Acid Transportersin Kidney, Liver, and Intestine of 5/6 Nephrecto-mized Rats. Hong Lu and Curtis Klaassen . . . . . 16

Disposition and Metabolism of [14C]Brasofensine inRats, Monkeys, and Humans. Mingshe Zhu,Daisy B. Whigan, Shu Y. Chang, and Randy C.Dockens . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Pharmacokinetics and Metabolism of 14C-Brivarac-etam, a Novel SV2A Ligand, in Healthy Subjects.Maria Laura Sargentini-Maier, Pascal Espie,Alain Coquette, and Armel Stockis . . . . . . . . . 36

Glucuronidation of Mycophenolic Acid by Wistar andMrp2-Deficient TR� Rat Liver Microsomes. IanS. Westley, Raymond G. Morris, Allan M. Evans,and Benedetta C. Sallustio . . . . . . . . . . . . . . 46

Hepatic UDP-Glucuronosyltransferases Responsiblefor Glucuronidation of Thyroxine in Humans.

Yoshihisa Kato, Shin-ichi Ikushiro, YoshikazuEmi, Sekihiro Tamaki, Hiroshi Suzuki, ToshiyukiSakaki, Shizuo Yamada, and Masakuni Degawa . 51

Regulation of CYP2A6 Protein Expression by Ska-tole, Indole, and Testicular Steroids in PrimaryCultured Pig Hepatocytes. Gang Chen, Rebecca-Ayme Cue, Kerstin Lundstrom, Jeffrey D. Wood,and Olena Doran . . . . . . . . . . . . . . . . . . . . . 56

Multidrug Resistance-Associated Protein 2 Is Primar-ily Responsible for the Biliary Excretion of Fexo-fenadine in Mice. Xianbin Tian, Maciej J. Zamek-Gliszczynski, Jun Li, Arlene S. Bridges, Ken-ichiNezasa, Nita J. Patel, Thomas J. Raub, and KimL. R. Brouwer . . . . . . . . . . . . . . . . . . . . . . . 61

Pharmacokinetics and Metabolic Profile of Free, Con-jugated, and Total Silymarin Flavonolignans inHuman Plasma after Oral Administration of MilkThistle Extract. Zhiming Wen, Todd E. Dumas,Sarah J. Schrieber, Roy L. Hawke, Michael W.Fried, and Philip C. Smith . . . . . . . . . . . . . . 65

Trimethoprim and the CYP2C8*3 Allele Have Oppo-site Effects on the Pharmacokinetics of Pioglita-zone. Aleksi Tornio, Mikko Niemi, Pertti J. Neu-vonen, and Janne T. Backman . . . . . . . . . . . . 73

Subdomain IIIA of Dog Albumin Contains a BindingSite Similar to Site II of Human Albumin. Ken-ichi Kaneko, Hikaru Fukuda, Victor Tuan GiamChuang, Keishi Yamasaki, Kohichi Kawahara,Hitoshi Nakayama, Ayaka Suenaga, Toru Ma-ruyama, and Masaki Otagiri . . . . . . . . . . . . . 81

Investigation of Regional Mechanisms Responsiblefor Poor Oral Absorption in Humans of a Modi-fied Release Preparation of the �-Adrenoreceptor

DRUG METABOLISMAND DISPOSITION

A Publication of the American Society for Pharmacology and Experimental Therapeutics

Drug Metabolism and Disposition (ISSN 0090-9556) is published monthly (one volume per year) by the American Society for Pharmacology and ExperimentalTherapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995; e-mail: info@aspet.org; Web site: http://www.aspet.org Periodicals postage paid at Bethesda, MD andat additional mailing offices. POSTMASTER: Send address changes to Drug Metabolism and Disposition, 9650 Rockville Pike, Bethesda, MD 20814-3995.Subscription rates: U.S.: $374.00 for institutions and $195.00 for non-ASPET members. Outside the U.S.: $448.00 for institutions and $269.00 for non-ASPETmembers. Single copy: $36.00. GST Tax Number for Canadian subscribers: BN:13489 2330 RT. Indexed or abstracted by Biochemistry & Biophysics CitationIndex®, Biological Abstracts, BIOSIS Previews Database, BioSciences Information Service, Current Awareness in Biological Sciences, Current Contents®/LifeSciences, EMBASE/Excerpta Medica, Index Medicus, International Pharmaceutical Abstracts, Medical Documentation Service®, Reference Update®, ResearchAlert®, Science Citation Index®, SciSearch®, and SIIC Data Bases. Copyright © 2008 by the American Society for Pharmacology and Experimental Therapeutics.All rights reserved. Printed in the U.S.A.

Continued on next page

Antagonist, 4-Amino-6,7-dimethoxy-2- (5-meth-anesulfonamido-1,2,3,4 tetrahydroisoquinol-2-yl)-5- (2-pyridyl)quinazoline (UK-338,003): TheRational Use of ex Vivo Intestine to Predict inVivo Absorption. A. Collett, R. H. Stephens, M.D. Harwood, M. Humphrey, L. Dallman, J. Ben-nett, J. Davis, G. L. Carlson, and G. Warhurst . 87

Regulation of Hepatic Drug-Metabolizing EnzymeGenes by Toll-Like Receptor 4 Signaling Is In-dependent of Toll-Interleukin 1 Receptor Do-main-Containing Adaptor Protein. Romi Ghose,Damara White, Tao Guo, Jesus Vallejo, and SaulJ. Karpen . . . . . . . . . . . . . . . . . . . . . . . . . . 95

Permeability, Transport, and Metabolism of Solutes inCaco-2 Cell Monolayers: A Theoretical Study.Huadong Sun and K. Sandy Pang . . . . . . . . . . 102

Effects of Chronic Renal Failure on Liver DrugTransporters. Judith Naud, Josee Michaud, Fran-cois A. Leblond, Stephane Lefrancois, Alain Bon-nardeaux, and Vincent Pichette . . . . . . . . . . . 124

Effect of Resveratrol on 17�-Estradiol Sulfation byHuman Hepatic and Jejunal S9 and RecombinantSulfotransferase 1E1. Anna M. Furimsky, CarolE. Green, Lewanne E. Hunt Sharp, Paul Catz,Araba A. Adjei, Toufan Parman, Izet M. Kapet-anovic, Richard M. Weinshilboum, and Lalitha V.Iyer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

HepaRG Cells as an in Vitro Model for Evaluation ofCytochrome P450 Induction in Humans. Kajsa P.Kanebratt and Tommy B. Andersson . . . . . . . . 137

The Influence of CYP3A5 Expression on the Extentof Hepatic CYP3A Inhibition Is Substrate-De-pendent: An in Vitro-in Vivo Evaluation. NinaIsoherranen, Shana R. Ludington, Raymond C.Givens, Jatinder K. Lamba, Susan N. Pusek, E.Claire Dees, David K. Blough, Kazunori

Iwanaga, Roy L. Hawke, Erin G. Schuetz, Paul B.Watkins, Kenneth E. Thummel, and Mary F.Paine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

Mechanism-Based Inactivation of Lung-Selective Cy-tochrome P450 CYP2F Enzymes. Jaya S. Karthaand Garold S. Yost . . . . . . . . . . . . . . . . . . . . 155

Identification of Cytochrome P450 Enzymes Involvedin the Metabolism of the New Designer Drug4�-Methyl-�-pyrrolidinobutyrophenone. Frank T.Peters, Markus R. Meyer, Denis S. Theobald, andHans H. Maurer . . . . . . . . . . . . . . . . . . . . . 163

Novel Single Nucleotide Polymorphisms in the Pro-moter and Intron 1 of Human Pregnane X Recep-tor/NR1I2 and Their Association with CYP3A4Expression. Jatinder Lamba, Vishal Lamba, Ste-phen Strom, Raman Venkataramanan, and ErinSchuetz . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

Transcription Factor and Drug-Metabolizing EnzymeGene Expression in Lymphocytes from HealthyHuman Subjects. Gerard Siest, Elise Jeannesson,Jean-Brice Marteau, Anastasia Samara, Be-rangere Marie, Michele Pfister, and Sophie Vis-vikis-Siest . . . . . . . . . . . . . . . . . . . . . . . . . . 182

Transport and Metabolism of Ferulic Acid through theColonic Epithelium. Laure Poquet, Michael N.Clifford, and Gary Williamson . . . . . . . . . . . . 190

Localization of P-gp (Abcb1) and Mrp2 (Abcc2) inFreshly Isolated Rat Hepatocytes. Daniel A. J.Bow, Jennifer L. Perry, David S. Miller, John B.Pritchard, and Kim L. R. Brouwer . . . . . . . . . 198

ERRATUM

Correction to “Use of Isolated Hepatocyte Prepara-tions for Cytochrome P450 Inhibition Studies:Comparison with Microsomes for Ki Determi-nation”. . . . . . . . . . . . . . . . . . . . . . . . . . . . 203

About the cover: Cister analysis of PXR (Fig. 1D). Regions with clusters of binding sites for liver-enriched transcriptionfactors and hormone receptors are indicated. See article by Lamba et al. on page 169 of this issue.

Contents (cont’d.)