TOC (PDF) - Drug Metabolism and Disposition - Aspetjournals.org

DRUG METABOLISM
AND DISPOSITION
A Publication of the American Society for Pharmacology and Experimental Therapeutics
September 2012 Vol. 40, No. 9
COMMENTARY
Nonspecific Protein Binding versus Membrane Partitioning:
It Is Not Just Semantics. Swati Nagar
and Ken Korzekwa .................... 1649
SHORT COMMUNICATION
Risk Assessment of Mechanism-Based Inactivation in
Drug-Drug Interactions. Yasushi Fujioka, Kent L.
Kunze, and Nina Isoherranen ............. 1653
ARTICLES
□S Progress Curve Mechanistic Modeling Approach for
Assessing Time-Dependent Inhibition of CYP3A4.
Howard J. Burt, Henry Pertinez, Carolina Säll,
Claire Collins, Ruth Hyland, J. Brian Houston, and
Aleksandra Galetin .................... 1658
A Novel Ring Oxidation of 4- or 5-Substituted 2H-
Oxazole to Corresponding 2-Oxazolone Catalyzed
by Cytosolic Aldehyde Oxidase. Vinod K.
Arora, Thomas Philip, Stella Huang, and Yue-
Zhong Shu ......................... 1668
□S Development of a Carbon-14 Labeling Approach to
Support Disposition Studies with a Pegylated Biologic.
Haiqing Wang, Lifei Wang, Kai Cao, Stuart
L. Emanuel, Paul Morin, Zheng Lin, Guoxiang
Shen, Jennifer Hosbach, Donglu Zhang,
Samuel Bonacorsi, A. David Rodrigues, and
Zheng Yang ........................ 1677
□S Selective Mechanism-Based Inactivation of CYP3A4
by CYP3cide (PF-04981517) and Its Utility as an
In Vitro Tool for Delineating the Relative Roles
of CYP3A4 versus CYP3A5 in the Metabolism
of Drugs. Robert L. Walsky, R. Scott Obach, Ruth
Hyland, Ping Kang, Sue Zhou, Michael West,
Kieran F. Geoghegan, Christopher J. Helal,
Gregory S. Walker, Theunis C. Goosen, and Michael
A. Zientek ..................... 1686
□S Evaluation of Six Proton Pump Inhibitors As Inhibitors
of Various Human Cytochromes P450: Focus
on Cytochrome P450 2C19. Tatyana Zvyaga,
Shu-Ying Chang, Cliff Chen, Zheng Yang, Ragini
CONTENTS
Vuppugalla, Jeremy Hurley, Denise Thorndike,
Andrew Wagner, Anjaneya Chimalakonda, and
A. David Rodrigues ................... 1698
□S Metabolism and Pharmacokinetics of Indacaterol in
Humans. Mark Kagan, Jeremy Dain, Lana Peng,
and Christine Reynolds ................. 1712
Excretion and Metabolism of Milnacipran in Humans
after Oral Administration of Milnacipran Hydrochloride.
Fanying Li, Christina Chin, Julie Wangsa,
and John Ho ........................ 1723
Role of Human UDP-Glucuronosyltransferases in the
Biotransformation of the Triazoloacridinone and
Imidazoacridinone Antitumor Agents C-1305
and C-1311: Highly Selective Substrates for
UGT1A10. Barbara Fedejko-Kap, Stacie M.
Bratton, Moshe Finel, Anna Radominska-Pandya,
and Zofia Mazerska ................ 1736
□S Use of Mechanistic Modeling to Assess Interindividual
Variability and Interspecies Differences in
Active Uptake in Human and Rat Hepatocytes.
Karelle Ménochet, Kathryn E. Kenworthy, J.
Brian Houston, and Aleksandra Galetin ..... 1744
Evaluation of P450 Inhibition and Induction by Artemisinin
Antimalarials in Human Liver Microsomes
and Primary Human Hepatocytes. Jie
Xing, Brian J. Kirby, Dale Whittington, Yakun
Wan, and David R. Goodlett ............. 1757
Mechanism-Based Inactivation of Cytochrome P450
2B6 by Methadone through Destruction of Prosthetic
Heme. Hemali T. Amunugama, Haoming
Zhang, and Paul F. Hollenberg ........... 1765
□S Quantitative Prediction of Human Intestinal Glucuronidation
Effects on Intestinal Availability of
UDP-Glucuronosyltransferase Substrates Using
In Vitro Data. Fumihiro Nakamori, Yoichi
Naritomi, Ken-ichi Hosoya, Hiroyuki Moriguchi,
Kazuhiro Tetsuka, Takako Furukawa, Keitaro
Kadono, Katsuhiro Yamano, Shigeyuki Terashita,
and Toshio Teramura .................. 1771
Continued on next page

Contents (cont’d.)
Metabolism of the Active Metabolite of Quetiapine,
N-Desalkylquetiapine In Vitro. Gry Vibeke Bakken,
Espen Molden, Karoline Knutsen, Niclas
Lunder, and Monica Hermann ............ 1778
Preclinical Assessment of the Absorption and Disposition
of the Phosphatidylinositol 3-Kinase/Mammalian
Target of Rapamycin Inhibitor GDC-0980
and Prediction of Its Pharmacokinetics and Efficacy
in Human. Laurent Salphati, Jodie Pang,
Emile G. Plise, Leslie B. Lee, Alan G. Olivero,
Wei Wei Prior, Deepak Sampath, Susan Wong,
and Xiaolin Zhang .................... 1785
Evaluation of Inhibition Selectivity for Human Cytochrome
P450 2A Enzymes. Eva S. Stephens, Agnes
A. Walsh, and Emily E. Scott .......... 1797
□S Discovery of a Highly Selective CYP3A4 Inhibitor
Suitable for Reaction Phenotyping Studies and
Differentiation of CYP3A4 and CYP3A5. Xiaohai
Li, Xinyi Song, Theodore M. Kamenecka, and
Michael D. Cameron .................. 1803
□S Preclinical Evaluation of the Metabolism and Disposition
of RRx-001, a Novel Investigative Anticancer
Agent. Jan Scicinski, Bryan Oronsky, Michael
Taylor, Gang Luo, Timothy Musick, Joseph
Marini, Christopher M. Adams, and William L.
Fitch ............................. 1810
Altered Arsenic Disposition in Experimental Nonalcoholic
Fatty Liver Disease. Mark J. Canet, Rhiannon
N. Hardwick, April D. Lake, Michael J.
Kopplin, George L. Scheffer, Walter T. Klimecki,
A. Jay Gandolfi, and Nathan J. Cherrington .. 1817
Characterization of SAGE Mdr1a (P-gp), Bcrp, and
Mrp2 Knockout Rats Using Loperamide, Paclitaxel,
Sulfasalazine, and Carboxydichlorofluorescein
Pharmacokinetics. Maciej J. Zamek-Gliszczynski,
David W. Bedwell, Jing Q. Bao, and J.
William Higgins ..................... 1825
□S Supplemental material is available online at http://dmd.aspetjournals.org.
□S The Role of Aldehyde Oxidase and Xanthine Oxidase
in the Biotransformation of a Novel Negative
Allosteric Modulator of Metabotropic
Glutamate Receptor Subtype 5. Ryan D. Morrison,
Anna L. Blobaum, Frank W. Byers,
Tammy S. Santomango, Thomas M. Bridges,
Donald Stec, Katrina A. Brewer, Raymundo
Sanchez-Ponce, Melany M. Corlew, Roger
Rush, Andrew S. Felts, Jason Manka, Brittney
S. Bates, Daryl F. Venable, Alice L. Rodriguez,
Carrie K. Jones, Colleen M. Niswender, P.
Jeffrey Conn, Craig W. Lindsley, Kyle A. Emmitte,
and J. Scott Daniels ............. 1834
Influence of Enterohepatic Recycling on the Time
Course of Brain-to-Blood Partitioning of Valproic
Acid in Rats. Jeannie M. Padowski and
Gary M. Pollack ..................... 1846
Glutaredoxin Is Involved in the Formation of the
Pharmacologically Active Metabolite of Clopidogrel
from Its GSH Conjugate. Katsunobu
Hagihara, Miho Kazui, Atsushi Kurihara, Toshihiko
Ikeda, and Takashi Izumi ............ 1854
ACCELERATED COMMUNICATION
A Novel Relay Method for Determining Low-Clearance
Values. Li Di, Patrick Trapa, R. Scott
Obach, Karen Atkinson, Yi-An Bi, Angela C.
Wolford, Beijing Tan, Thomas S. McDonald, Yurong
Lai, and Larry M. Tremaine .......... 1860
ERRATA
Correction to “Identification of Novel Metoclopramide
Metabolites in Human: In Vitro and In Vivo
Studies” ........................... 1866
Correction to “Identification and Validation of Novel
Human Pregnane X Receptor Activators among
Prescribed Drug via Ligand-Based Virtual
Screening” .......................... 1868
About the cover: Schematic representation of a 40-kDa branched PEGylated Adnectin (P40BEI-tandem). See the article by
Wang et al. on page 1677 of this issue.