Drug Metabolism and Disposition: the biological fate of chemicals

January/February 1991 Vol. 19, No. 1 CONTENTS

Pharmacokinetics of 4-Hydroxycyclophosphamide and B. FRANKLIN 54 Metabolites in the Rat. PHILLIP S. HONG, AEUM- PORN SRIGRITSANAPOL, AND KENNETH K. CHAN Effects of Age and Dose on the Pharmacokinetics of Ibuprofen in the Rat. JULIA H. SATTERWHITE AND Kinetics of Distribution and Adipose Tissue Storage as F. DOUGLAS BOUDINOT 61

a Function of Lipophilicity and Chemical Struc- Downloaded from ture. I. Barbiturates. S. H. STEINER, M. J. MooR. Disposition of the Cephalosporin Cefepime in Normal AND M. H. BICKEL 8 and Renally Impaired Subjects. R. H. BARBHAIYA, C. A. KNUPP, S. T. FORGUE. 0. R. MATZKE, C. E. Kinetics of Distribution and Adipose Tissue Storage as HALSTENSON, J. A. OPSAHL, AND K. A. PITTMAN . 68 a Function of Lipophilicity and Chemical Struc- ture. II. Benzodiazepines. X. XIE, S. H. STEINER, The Enzymatic Hydrolysis-Activation of the Adriamy- AND M. H. BICKEL 15 cm Cardioprotective Agent (+)-l,2-Bis(3,5-dioxo- dmd.aspetjournals.org piperazinyl- l-yI)propane. BRIAN B. HASINOFF, Glucuronidation of Labetalol at the Two Hydroxy Po- FRANCIS X. REINDERS, AND VIVIEN CLARK 74 sitions by Bovine Liver Microsomes: Isolation, Pu- rification, and Structure Elucidation of the Glu- The Metabolism of 3,7-Dimethyl-2,6-octadienal (Ci- curonides of Labetalol. Nico R. NIEMEIJER, THIJS tral) in Rat Hepatic Mitochondrial and Cytosolic K. GERDING, AND ROKUS A. DE ZEEUW 20 Fractions: Interactions with Aldehyde and Alcohol Redistribution of Tncyclic Antidepressants in Rats Us- Dehydrogenases. C. SCOTT BOYER AND DENNIS R. ing a Drug-Specific Monoclonal Antibody: Dose- PETERSON 81 at ASPET Journals on September 25, 2021 Response Relationship. PAUL R. PENTEL, DANIEL Prednisolone and Prednisone Exhibit Linear Extraction E. KEYLER, GREGORY J. BRUNN, JAMES M. MILAV- in the Perfused Rabbit Liver. VICrORIA 0. HALE ETZ, DEBRA G. GILBERTSON, SHANNON 0. MATTA. AND LESLIE Z. BENET 87 AND SUSAN M. POND 24 Biodistribution and Metabolism in Rats and Mice of Comparative Pharmacokinetics of Abecarnil in Rat Bucromarone. J. C. MAURIZIS. C. NICOLAS, M. Following Single and Multiple Intragastric Treat- VERNY, M. OLLIER, M. FAURIE, M. PAYARD, AND ment and Continuous Administration Via the A. VEYRE 94 Diet. W. KRAUSE, F. REI/3MANN, W. SCHUNACK, AND CHR. SCHOBEL 29 Purification of Human Serum Paraoxonase/Arylester- ase: Evidence for One Esterase Catalyzing Both Metabolites, Pharmacoclynamics, and Pharmacoki- Activities. KAREN N. GAN, ANDREW SMOLEN, netics of Tamoxifen in Rats and Mice Compared HARRY W. ECKERSON, AND BERT N. LA DU 100 to the Breast Cancer Patient. SIMON P. ROBINSON, SUSAN M. LANGAN-FAHEY, DELINDA A. JOHNSON, Characteristics of the Genetically Determined Allo- AND V. CRAIG JORDAN 36 zymic Forms of Human Serum Paraoxonase/ Arylesterase. ANDREW SMOLEN, HARRY W. ECK- In Vitro and In Vivo Murine Metabolism of Spiroger- ERSON, KAREN N. GAN, NABIL HAII.AT, AND BERT manium. D. GARTEIZ, Z. H. SIDDIK, AND R. A. N. LA DU 107 NEWMAN 44 1mm unohistochemical Localization of Cytochrome P- Genetic Polymorphism of Cytochrome P-450-Depend- 4501A 1 Induced by 3,3’,4.4’-Tetrachlorobiphenyl ent Phencyclidine Hydroxylation in Mice: Com- and by 2,3,7,8-Tetrachlorodibenzofuran in Liver parison to Phencyclidine Hydroxylation in Hu- and Extrahepatic Tissues of the Teleost Stenotomus mans. ELZBIETA J. HOLSZTYNSKA, WENDELL W. chrrsops (Scup). ROXANNA M. SMoLowlTz, MARK WEBER, AND EDWARD F. DOMINO 48 E. HAHN, AND JOHN J. STEGEMAN 113 Observations on the Absorption, Distribution, Metab- Metabolism of Dibasic Esters by Rat Nasal Mucosal olism, and Excretion of the Dopamine (D2) Ago- Carboxylesterase. MATTHEW S. BOGDANFFY, CE- nist, Quinelorane, in Rats, Mice, Dogs, and Mon- CILIA R. KEE, CHERI A. HINCHMAN, AND BRUCE keys. B. M. MANZIONE, J. R. BERNSTEIN, AND R. A. TRELA 124 (‘ontititied on iie.vt pa,’e

DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is an official publication of the American Society for Pharmacology and Experimental Therapeutics and is published bimonthly by williams & Wilkins. 428 E. Preston St.. Baltimore. MD 2 1202-3993. Second class postage paid at Baltimore. MD and at additional mailing offices. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION. 428 E. Preston St., Baltimore. MD 2 1202-3993. Price per volume: USA individual rate $75: all other countries $95 surface mail. USA institutional rate $120: all other countries $140 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Indexed by Jndev Medicus. Current (onu’nis/Life Sciences. BioSciences Information Service, and Evcerpta Medico. Copyright (d 991 by the American Society for Pharmacology and Experimental Therapeutics. (‘onlents (cot,! ‘ci,)

Chronic Stress Impairs Oxidative Metabolism and He- Metabolism and Disposition of Sulfiuramid, a Unique patic Excretion of Model Xenobiotic Substrates in Polyfluorinated Insecticide, in the Rat. RANDALL the Rat. GARY M. POLLACK, JERRY L. BROWNE, 0. MANNING, JAMES V. BRUCKNER, MICHAEL E. JENO MARTON, AND LYNDA J. HABERER 130 MISPAGEL, AND JOHN M. BOWEN 205

[4C]Monocrotaline Kinetics and Metabolism in the Disposition and Metabolism of the Angiotensin-Con- Rat. JAMES E. ESTEP, MICHAEL W. LAM#{201},DEXTER veIling Enzyme Inhibitor [4S-[4a, 7a, (R*), 12b3]] MORIN, A. DANIEL JONES, DENNIS W. WILSON, 7-[S-( 1-Ethoxycarbonyl-3-phenylpropyl)amino]- AND H. J. SEGALL 135 I ,2,3,4,6,7,8, I 2b-octahydro-6-oxo-pyrido[2, l-aJ [2] Benzazepine-4-Carboxylic Acid in Monkeys Evidence for Glucuronidation and Sulfation of Zeranol and Dogs. HAIYUNG CHENG, JOHN D. STUHLER, and Metabolites (Taleranol and Zearalanone) by BRUCE R. DORRBECKER, AND W. PERRY GORDON 212 Rat and Pig Hepatic Subfractions. 0. F. BORIES, E. F. PERDU-DURAND, J. F. SUTRA, AND J. E. TULLIEZ Mouse Hepatic Microsomal Enzyme That Catalyzes 140 Oxidation of I 1-Oxo-.\8-Tetrahydrocannabinol to 8-Tetrahydrocannabinol-l l-oic Acid. KAZUHITO Gastrointestinal Absorption of Xenobiotics in Physio- WATANABE, NORIKO HIRAHASHI, SHIZUO NARI- logically Based Pharmacokinetic Models: A Two- MATSU, IKUO YAMAMOTO, AND HIDETOSHI Compartment Description. D. A. STAATS, J. W. YOSHIMURA 218

FISHER, AND R. B. CONNOLLY 144 Downloaded from Identification of Thiodiglycolic Acid, Thiodiglycolic Isolation and Identification ofa Novel Quaternary Am- Acid Sulfoxide, and (3-Carboxymethylthio)Lactic monium-Linked Glucuronide of Lamotrigine. MI- Acid as Major Human Biotransformation Products CHAEL W. SINZ AND RORY P. REMMEL 149 of S-Carboxymethyl-L-Cysteine. UTE HOFMANN, Cis-Flupentixol Metabolites in Rat Plasma and Bile: MICHEL EICHELBAUM, SONJA SEEFRIED, AND The First Proof of Glutathione Conjugation at the CLAUS 0. MEESE 222 Exocyclic Double Bond. YUE-ZHONG SHU, JOHN dmd.aspetjournals.org Xenobiotic Metabolizing Enzyme Activities in Rat, W. HUBBARD, GORDON MCKAY, EDWARD M. Mouse, Monkey, and Human Testes. KAREN W. HAWES, AND KAMAL K. MIDHA 154 DIBIASIO, MARILYN H. SILVA, LEE R. SHULL, Pharmacokinetics and Metabolism of Triclopyr in the JAMES W. OVERSTREET, BRUCE D. HAMMOCK, AND Crayfish (Procamharus clarki). M. 0. BARRON, S. MARION 0. MILLER 227 C. HANSEN, AND T. BALL 163 Dose-Dependent Stereopharmacokinetics of 5,6-Dihy- Study of the Placental Transfer of Cisapride in Sheep: dro-4H-4(isobutylamino)-thieno(2,3-B)thiopyran- at ASPET Journals on September 25, 2021 Plasma Levels in the Pregnant Ewe, the Fetus, and 2-sulfonamide-7,7-dioxide, a Potent Carbonic An- the Lamb. GENEVIEVE VEEREMAN-WAUTERS, Jo- hydrase Inhibitor, in Rats. JIUNN H. LIN, EDGAR HAN MONBALIU, WILLEM MEULDERMANS, ROBERT H. ULM, AND LAYNE E. Los 233 WOESTENBORGHS, MARLEEN VERLINDEN, JOSEPH Studies on Induction of Metabolism of Ethyl Carba- HEYKANTS, AND COLIN D. RUDOLPH 168 mate in Mice by Ethanol. NORIMITSU KURATA, Glucuronidation of Monohydroxylated Short Chain HARRELL E. HURST, RAYMOND A. KEMPER, AND Bile Acids by Human Liver Microsomes and Pu- WILLIAM J. WADDELL 239 rifled Human Liver UDP-Glucuronosyltransfer- Temporal Variations in Microsomal Lipid Peroxidation ases. YACOUB M. IRSHAID, ANNA RADOMINSKA, and in Glutathione Concentration of Rat Liver. PIOTR ZIMNIAK, ANDRZEJ ZIMNIAK, ROGER LES- PIERRE M. BELANGER, MARC DESGAGNE, AND TER, AND THOMAS R. TEPHLY 173 BERNARD BRUGUEROLLE Identification of Major Metabolites of the Catechol-O- Methyltransferase-Inhibitor Nitecapone in Human Dose-Dependent and Time-Dependent Pharmacoki- netics in the Dog after Intravenous Administration Urine. JYRKI TASKINEN, TOM WIKBERG, PEKKA OTTOILA, LIISA KANNER, TIM0 LOTTA, AINO Pie- of Dextrorphan. P. A. CLEVELAND, S. TELLER, V. KACHEVSKY, E. PINILI, R. EVANS, AND M. W. PURl, AND REIJO BACKSTROM 178 MODI 245 Mechanism of Acetaminophen-Stimulated NADPH Oxidation Catalyzed by the Peroxidase-H2O2 Sys- Stereoselective Differences in Propranolol Disposition in Female Sprague-Dawley and Dark Agouti Rats. tem. RANDAL J. KELLER AND JACK A. HINSON .. 184 ROBERT J. GUTTENDORF, HARRY B. KOSTENBAU- Identification of Phase-I and Phase-Il Metabolites of DER, AND PETER J. WEDLUND 251 Fluphenazine in Rat Bile: Intact Glucuronide and Sulfate Conjugates. C.-J. C. JACKSON, J. W. HUB- Metabolism and Penetration through Blood-Brain Bar- BARD, 0. MCKAY, J. K. COOPER, E. M. HAWES, rier of Parkinsonism-Related Compounds: 1,2,3,4- AND K. K. MIDHA 188 Tetrahydroisoquinoline and l-Methyl-l,2,3,4-te- trahydroisoquinoline. KAZUYA KIKUCHI, YOSHIO Role of the Endopeptidase 24.11 in the Disposition and NAGATSU, YUKIKO MAKINO, TADAHIKO MASHINO, Metabolism of Endogenous Atrial Natriuretic Fac- SHIGERU OHTA, AND MASAAKI HIROBE 257 tor in the Rabbit. SYLVIE MARLEAU, TIEN-TUE NGUYEN, PATRICK Du SOUICH, MONIQUE BELLE- Characterization of the Urinary Metabolites of Merba- MARE. ANDRE DE LEAN, AND HUY ONG 194 rone in Cancer Patients. JEFFREY G. SUPKO AND Louis MALSPEIS 263 Pharmacokinetics of Recombinant Human Granulo- cyte Colony-Stimulating Factor in the Rat: Single Biosynthesis and Biliary Excretion of S-Conjugates of and Multiple Dosing Studies. HIDEJI TANAKA AND Hexachlorobuta- 1 ,3-diene in the Perfused Rat TATSUHIKO KANEKO 200 Liver. Y. S. GIETL AND M. W. ANDERS 274

continued on next nape Contents (cont ‘d)

SHORT COMMUNICATIONS and Intramuscular Administration. CLAUDE L. WOODARD AND BRIAN J. LUKEY 283

Vitamin K Epoxide Reductase Activity and its Inhibi- Circadian Variation of Fluoropyrimidine Catabolic tion by Warfarin in Young and Old Rats. HUSSEIN Enzymes in Rat Liver: Possible Relevance to 0. HALLAK AND PETER J. WEDLUND 278 5-Fluorodeoxyuridine Chemotherapy. GEORGE C. DAHER, RUIWEN ZHANG, SENG-JAW SOONG, AND Stereoselective Hydrolysis of Flurbiprofen Conjugates. ROBERT B. DIASIO 285 M. P. KNADLER AND S. D. HALL 280 Books Received 288

MMB-4 Pharmacokinetics in Rabbits after Intravenous Erratum 289 Downloaded from dmd.aspetjournals.org at ASPET Journals on September 25, 2021 Drug Metabolism and Disposition: the biological fate of chemicals

March/April 1991 Vol. 19, No. 2 CONTENTS

Purification and Aminopyrine Monooxygenase Activ- KENNETH E. THUMMEL, THOMAS F. KALHORN, ity of Liver Microsomal Cytochrome P-450 from SIDNEY D. NELSON, AND JOHN T. SLATTERY .... 348 Alloxan-Induced Diabetic Rats. HIR0SHI SHIMENO, Oxidation of Propylthiouracil to Reactive Metabolites AKIHISA TODA, SHIGENORI OGATA, AND ATSUO by Activated Neutrophils: Implications for NAGAMATSU 291 Agranulocytosis. LISA WALDHAUSER AND JACK Downloaded from

Oxidation of 1 , 1 , 1,2-Tetrafluoroethane in Rat Liver UETRECHT 354 Microsomes is Catalyzed Primarily by Cytochrome Model Systems for Metabolism Studies: Biomimetic P-4501IE1. MICHAEL J. OLSON, SANG GEON KIM, Oxidation of Acetaminophen and Ellipticine De- CHARLES A. REIDY, JOHN T. JOHNSON, AND RAY- rivatives with Water-Soluble Metalloporphyrins MOND F. NOVAK 298 Associated to Potassium Monopersulfate. J. BER- Stereoselective (5)- and (R)-Naproxen Glucuronosyl- NADOU, M. BONNAFOUS, 0. LABAT, P. LOISEAU, transferases of Rat Liver. MOHAMED EL MOUELHI AND B. MEUNIER 360 dmd.aspetjournals.org AND KARL WALTER BOCK 304 Metabolism and Disposition ofp-Chloroaniline in Rat, The Pharmacokinetics of Albumin Conjugates of D- Mouse, and Monkey. WILLIAM J. EHLHARDT AND Penicillamine in Humans. DAVID A. JOYCE, RICH- J. JEFFRY HOWBERT 366 ARD 0. DAY, AND BARBARA R. MURPHY 309 Metabolism and Disposition of the Anticancer Agent Effect of H2 Antagonists on the Differential Secretion Sulofenur in Mouse, Rat, Monkey, and Human. of Triamterene and its Sulfate Conjugate Metabo- WILLIAM J. EHLHARDT 370 at ASPET Journals on September 25, 2021 lite by the Isolated Perfused Rat Kidney. MURRAY Stereoselective Glucuronidation of Ofloxacin in Rat R. MUIRHEAD AND ANDREW A. SoMoiYI 312 Liver Microsomes. OSAMU OKAZAKI, TADASHI Plasma Pharmacokinetics and Metabolism of I 3-Cis- KURATA, HIDEO HAKUSUI, AND HARUO TACHI- and all-Trans-Retinoic Acid in the Cynomolgus ZAWA 376 Monkey and the Identification of 13-Cis- and All- The Metabolism of [‘4ClRimantadine Hydrochloride Trans-Retinoyl-f3-Glucuronides: A Comparison to in Rats and Dogs. A. C. L0H, A. J. SZUNA, T. H. One Human Case Study with Isotretinoin. J. WILLIAMS, 0. J. SASSA, AND F.-J. LEINWEBER ... 381 CREECH KRAFT, W. SLIKKER, JR., J. R. BAILEY, L. G. ROBERTS, B. FISCHER, W. WITTFOHT, AND Studies on Inhibition and Induction of Metabolism of H.NAU 317 Ethyl Carbamate by Acetone and Related Com- pounds: Evidence for Metabolism by Cytochrome The Detection of Halocarbon-Derived Radical Adducts P-450. NORIMITSU KURATA, HARRELL E. HURST, in Bile and Liver of Rats. KATHRYN T. KNECHT FREDERICK W. BENZ, RAYMOND A. KEMPER, AND AND RONALD P. MASON 325 WILLIAM J. WADDELL 388 Conversion of Retinol to Retinal by Rat Liver Micro- Metabolism of the Antipsychotic Drug Tiospirone in somes. T. W. SHIH AND D. L. HILL 332 Humans. ROBERT F. MAYOL, HEMANT K. JAJOO, Conversion of Retinoid Ethers to Alcohols by Enzy- LEWIS J. KLUNK, AND IAN A. BLAIR 394 matic Activity Present in Rat Liver Microsomes. Correlation between Plasma Physostigmine Concentra- T. W. SHIH, Y. F. SHEALY, AND D. L. HILL 336 tions and Percentage of Acetylcholinesterase Inhi- Intestinal Biotransformation of Harmol and 1-Naph- bition over Time after Controlled Release of Phy- thol in the Rat: Further Evidence of Dose-Depend- sostigmine in Volunteer Subjects. S. KNAPP, M. L. ent Phase-Il Conjugation In Situ. DANIEL GOON WARDLOW, KEN ALBERT, DON WATERS, AND AND CURTIS D. KLAASSEN 340 L. J. THAL 400 Inhibition and Activation of Acetaminophen Reactive Mechanistic Studies on the Metabolic Chiral Inversion Metabolite Formation by Caffeine: Roles of Cyto- of R-Ibuprofen in the Rat. SUSAN M. SANINS, chromes P-450IAl and 111A2. CAROLINE A. LEE, WADE J. ADAMS, DAVID 0. KAISER, GORDON W. continued on next page

DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is an official publication of the American Society for Pharmacology and Experimental Therapeutics and is published bimonthly by Williams & Wilkins. 428 E. Preston St.. Baltimore. MD 2 1202-3993. Second class postage paid at Baltimore. MD and at additional mailing offices. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION. 428 E. Preston St.. Baltimore. MD 21202-3993. Price per volume: USA individual rate $75: all other countries $95 surface mail. USA institutional rate $120: all other countries $140 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Indexed by Index Medicus. (‘urren! Contents/Li/i’ Sciences. BioSciences Information Service, and Excerpia Medico. Copyright c 1991 by the American Society for Pharmacology and Experimental Therapeutics. contents (con! ‘d.)

HALSTEAD, JOHN HOSLEY, HOPE BARNES, AND Potential Error in the Measurement of Tissue to Blood THOMAS A. BAILLIE 405 Distribution Coefficients in Physiological Phar- macokinetic Modeling: Residual Tissue Blood. II. Comparative Disposition and Metabolism of 1,2,3- Distribution of Phencyclidine in the Rat. 500 Trichloropropane in Rats and Mice. NIK A. MAH- PEANG KHOR, HAIG BOZIGIAN, AND MICHAEL MOOD, DIANE OVERSTREET, AND LEO T. BURKA . 411 MAYERSOHN 486

Urinary and Biliary Excretion of Metabolites of Halo- Disposition, Metabolism, and Excretion ofthe Antican- thane in Dogs. TAKAYUKI SAKAI, HIT0SHI Yo- cer Agent Crisnatol in the Rat. DIPAK K. PATEL, SHIDA, AKIRA FUKUI, AND MASUHIKO TAKAORI . 419 JOSEPH L. WOOLLEY, JR., JOHN P. SHOCKCOR, RoB- Phenacetin and Acetaminophen Metabolism in the Iso- ERT L. JOHNSON, LESTER C. TAYLOR, AND CARL lated Perfused Rat Liver: Precursor Concentration W. SIGEL 491 Influences the Selection of Kinetic Parameters to Drug Metabolizing Enzyme Changes after Chronic Assess Hypoxic Impairment. SCOTT D. STUDEN- Buthionine Sulfoximine Exposure Modify Aceta- 423 BERG AND KIM L. R. BROUWER minophen Disposition in Rats. BRADFORD W. Pharmacokinetics of Theophylline in the Newborn and MANNING, MICHAEL R. FRANKLIN, AND RAY- Adult Rabbit: In Vivo and Isolated Perfused Liver MONDE.GALINSKY 498 Approaches. ANGELA BORTOLOTTI, MONICA Co- Kinetics of Acetyl CoA: Arylamine N-Acetyltransferase Downloaded from RADA, MARIA MONICA BARZAGO, ANTONIO from Rapid and Slow Acetylator Human Liver. CELARDO, AMALIA GUAITANI, AND MAURIZIO ANTHONY J. KILBANE, THOMAS PETROFF, AND BONATI 430 WENDELL W. WEBER 503 Brain Distribution and Fate of Tris(2-Chloroethyl) Formation of N-(5-Nitro-2-thiazolyl-N’-carboxymeth- Phosphate in Fischer 344 Rats. D. W. HERR, J. M. ylurea from 5-Hydroxyniridazole: Role of Alde- SANDERS, AND H. B. MATTHEWS 436 hyde Dehydrogenase in the Oxidative Metabolism dmd.aspetjournals.org Metabolism of Tris(2-Chloroethyl) Phosphate in Rats ofNiridazole. JAMES W. TRACY, BRIAN A. CATrO, and Mice. L. T. BURKA, J. M. SANDERS, D. W. AND LESLIE T. WEBSTER, JR 508 HERR, AND H. B. MATTHEWS 443 Metabolism of[’4C]Monocrotaline by Isolated Perfused Stereoselective Sulfate Conjugation of Racemic 4-Hy- Rat Liver. MICHAEL W. LAM#{201},A. DANIEL JONES, droxypropranolol by Human and Rat Liver Cyto- DEXTER MORIN, AND H. J. SEGALL 516 sol. T. WALLE AND U. K. WALLE 448 Identification and Characterization of the Glutathione and N-Acetylcysteine Conjugates of (E)-2-Propyl- Metabolism of 7-( 1,3-Dithiolan-2-ylmethyl)- 1,3-di- at ASPET Journals on September 25, 2021 methylxanthine by Rat Liver Microsomes: Dia- 2,4-pentadienoic Acid, a Toxic Metabolite of Val- stereoselective Metabolism of the 1 ,3-Dithiolane proic Acid, in Rats and Humans. KELEM K&sSA- Ring. GIORGIO GROSA, OTTO CAPUTO, MAURIZIO HUN, KEVIN FARRELL, AND FRANK ABBOTT . ... 525 CERUTI, GIUSEPPE BIGLINO, JOS#{201}SEBASTIAN FRAN- Rapid, Dose-Dependent Elimination of Phenol Across ZONE, AND CARLO CRAVANZOLA 454 the Gills, and Slow Elimination of Phenyl Sulfate Meta-Hydroxymexiletine, A New Metabolite of Mexi- in the Urine, of Phenol-Dosed Lobsters, Homarus letine: Isolation, Characterization, and Species Dif- americanus. MARGARET 0. JAMES, JOHN D. ferences in its Formation. ODETTE GRECH- SCHELL, MACE 0. BARRON, AND CHUNG-LI J. LI 536 BELANGER, JACQUES TURGEON, MARCEL LA- Inhibition of Aryl Sulfotransferase by Carboxylic Acids. LANDE, AND PIERRE M. BELANGER 458 SATISH I. RAO AND MICHAEL W. DUFFEL 543

(-)-6-Aminocarbovir Pharmacokinetics and Relative Pharmacokinetics of Butixocort 21 -Propionate, Bude- Carbovir Exposure in Rats. RUSSELL L. YEAGER, sonide, and Beclomethasone Dipropionate in the KENNETH R. BROUWER, AND GERALD T. MIWA . 462 Rat after Intratracheal, Intravenous, and Oral Oxidation of Butylated Hydroxytoluene to Toxic Me- Treatments. F. CHANOINE, C. GRENOT, P. HElD- tabolites: Factors Influencing Hydroxylation and MANN, AND J. L. JUNIEN 546 Quinone Methide Formation by Hepatic and Pul- monary Microsomes. JUDY L. BOLTON AND JOHN A. THOMPSON 467 SHORT COMMUNICATIONS Biotransformation of the Organophosphorus Insecti- cides Parathion and Methyl Parathion in Male and Female Rat Livers Perfused In Situ. HUI XING Binding Interaction between Enantiomers of Disopyr- ZHANG AND LESTER G. SULTATOS 473 amide and Mono-N-dealkyldisopyramide on Plasma Protein. HARUMI TAKAHASHI, HIROYASU Potential Error in the Measurement of Tissue to Blood OGATA,ANDYUMIKOSEKI 554 Distribution Coefficients in Physiological Phar- macokinetic Modeling: Residual Tissue Blood. I. Mechanisms by Which Acetaminophen Administration Theoretical Considerations. 500 PEANG KHOR AND Diminishes Ethanol Clearance. JOHN T. SLATTERY, MICHAEL MAYERSOHN 478 THOMAS F. KALHORN, AND KENNETH E. THUMMEL 558 Drug Metabolism and Disposition: the biological fate of chemicals

May/June 1991 Vol. 19, No. 3 CONTENTS

Evidence for the Involvement of Several Cytochromes Glutathione Conjugation with Phosphoramide Mustard P-450 in the First Steps ofCaffeine Metabolism by and Cyclophosphamide: A Mechanistic Study Us- Human Liver Microsomes. FRANc0I5 BERTHOU, ing Tandem Mass Spectrometry. ZHI-MIN YUAN, JEAN-PIERRE FLINOIS, DAMRONG RATANASAVANH, P. B. SMITH, R. B. BRUNDRETT, MICHAEL COLVIN, PHILIPPE BEAUNE, CHRISTIAN RICHE, AND ANDR#{201} AND CATHERINE FENSELAU 625 GUILLOUZO 561 A Quaternary Ammonium Glucuronide is the Major Downloaded from Enzymatic Detoxification of Phosphoramide Mustard Metabolite of Lamotrigine in Guinea Pigs: In Vitro by Soluble Fractions from Rat Organ Tissues. and In Vivo Studies. RORY P. REMMEL AND PHILLIP S. HONG AND KENNETH K. CHAN 568 MICHAEL W. SINZ 630

The Disposition and Pharmacokinetics of Alpidem, Stereoselective Metabolism of Prazepam and Halaze- a New Anxiolytic, in the Rat. D. GARRIGOU- pam by Human Liver Microsomes. XIANG-LIN Lu, GADENNE, A. DURAND, J. P. THENOT, AND P. L. PETER GUENGERICH, AND SHEN YANG ....

F. K. 637 dmd.aspetjournals.org MORSELLI 574 1, l-Dichloroethylene Elicits Dose-Dependent Altera- Clinical Pharmacology of l-fl-D-Arabinofuranosyl-5- azacytosine (Fazarabine) following 72-Hour Infu- tions in Covalent Binding and Glutathione in Mu- sion. DAH H. Ho, NITA BROWN, JUAN R. LIN, rine Liver. P. GEK FORKERT AND MADELEINE WENDY COVINGTON, ROBERT A. NEWMAN, MAR- MOUSSA 580 TIN RABER, ROBERT AMATO, SUE SCHMIDT, AND IRWIN H. KRAKOFF 643 Biotransformation of Territrems by S Fraction from

Rat Liver. Kuo HUANG LING, CHI MING CHI0U, at ASPET Journals on September 25, 2021 The N-Acetylation ofSulfamethazine and p-Aminoben- AND YUN LONG TSENG 587 zoic Acid by Human Liver Slices in Dynamic Geometric Isomerization of Doxepin during its N- Organ Culture. L. GUNAWARDHANA, J. BARR, Demethylation in Humans. HANY GHABRIAL, A. J. WEIR, K. BRENDEL, AND I. G. SIPES 648 CHANDRA PRAKASH, ULRICH G. TACKE, IAN A. BLAIR, AND GRANT R. WILKINSON 596 Physiological Pharmacokinetic and Pharmacodynamic Model of Physostigmine in the Rat. SATU M. So- The Disposition and Metabolism of [‘4C]Piritrexim in MANI, SAMIR K. GUPTA, ABDUL KHALIQUE, AND Rats after Intravenous and Oral Administration. LATHA K. UNNI 655 JOSEPH L. WOOLLEY, DIANE V. DEANGELIS, RON- ALD C. CROUCH, JOHN P. SHOCKCOR, AND CARL Metabolism and Pharmacokinetics of 1,3-Dinitroben- W. SIGEL 600 zene in the Rat and the Hamster. STEVEN F. MCEUEN AND MARION G. MILLER 661 Enantioselective Hydrolysis of Lorazepam 3-Acetate by

Esterases in Human and Rat Liver Microsomes Disposition Kinetics and Metabolism of Nicotine-l ‘- and Rat Brain S9 Fraction. K.N LIU, F. PETER N-Oxide in Rabbits. MIN JIANG DUAN, LISA Yu, GUENGERICH, AND SHEN K. YANG 609 CHIN SAVANAPRIDI, PEYTON JACOB, III, AND NEAL L. BENOWITZ 667 The Pharmacokinetics of Dobutamine in Pediatric In- tensive Care Unit Patients. PHILIP H. SCHWARTZ, Low Dose Chlordecone Pretreatment Altered Choles- MAHER K. ELDADAH, AND CHRISTOPHER J. L. terol Disposition without Induction of Cytochrome NEWTH 614 P-450. HILLARY M. CARPENTER AND LAWRENCE Nordihydroguaiaretic Acid, an Inhibitor of Lipoxygen- R. CURTIS 673 ase, also Inhibits Cytochrome P-450-Mediated Mechanisms Responsible for the Thermal Sensitivity of Monooxygenase Activity in Rat Epidermal and Adrenal Microsomal Monooxygenases. HOWARD Hepatic Microsomes. RAJESH AGARWAL, ZHI Y. D. COLBY, PEGGY B. JOHNSON, AND MARLENE R. WANG, DANIEL P. BIK, AND HASAN MUKHTAR 620 POPE 679

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DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is an official publication of the American Society for Pharmacology and Experimental Therapeutics and is published bimonthly by Williams & Wilkins, 428 E. Preston St., Baltimore, MD 2 1202-3993. Second class postage paid at Baltimore, MD and at additional mailing offices. The GST Tax Number for Canadian subscribers is 123394371. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 2 1202-3993. Price per volume: USA individual rate $75; all other countries $95 surface mail. USA institutional rate $120: all other countries $140 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Indexed by Index Medicus, Current Contents/Life Sciences. BioSciences Information Service, and Excerpia Medica. Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics. Contents (cont ‘d)

Degradation of Peptide Drugs by Immobilized Diges- Comparative Study of Phase II Biotransformation in tive Proteases. RICHARD B. VAN BREEMEN, MI- Rabbit Ocular Tissues. JOHN B. WATKINS, III, CHAEL 0. BARTLETT, YINHSIEN Tsou, CATHERINE DARREN P. WIRTHWEIN, AND RUTH A. SANDERS 708 CULVER, HAROLD SWAIS000D, AND STEVE E. UNGER 683

Determination of Metabolically Derived Nitroprocain- SHORT COMMUNICATIONS amide in the Urine of Procainamide-Dosed Hu- In Vitro Metabolism of the Equatorial C, ,-Methyl Iso- mans and Rats by Liquid Chromatography with mer of Hexahydrocannabinol in Several Mamma- Electrochemical Detection. JOHN F. WHEELER, lian Species. D. J. HARVEY AND N. K. BROWN .. 714 LOUIS E. ADAMS, ANNE-BARBARA MONGEY, STEPHEN M. ROBERTS, WILLIAM R. HEINEMAN, Stereoselective Disposition of Ketoprofen in Rats. AND EVELYN V. HLsS 691 SEIGO IWAKAWA, XIWEN HE, SUMIKO HASHIMOTO, CHRISTINE VOLLAND, LESLIE Z. BENET, AND EMIL Metabolism of the Acyl-Coa:Cholesterol Acyltransfer- T. LIN 717 ase Inhibitor 2,2-Dimethyl-N-(2,4,6-trimethoxy- phenyl)dodecanamide in Rat and Monkey: w-/f3- Chronic Administration of Phencyclidine: Pharmaco- Oxidation Pathway. THOMAS F. WOOLF, SUSAN M. kinetic Comparison of Intravenous and Subcuta- BJORGE, ANN E. BLACK, ANN HOLMES, AND TSUN neous Infusions in Sprague-Dawley Rats. WILLIAM

CHANG 696 D. WESSINGER AND S. MICHAEL OWENS 719 Downloaded from

Intestinal Absorption of S-(Pentachlorobutadienyl) The Quaternary Ammonium-Linked Glucuronide of glutathione and S-(Pentachlorobutadienyl)-L-cys- Doxepin: A Major Metabolite in Depressed Pa- teine, the Glutathione and Cysteine S-Conjugates tients Treated with Doxepin. H. Luo, E. M. of Hexachlorobuta-l,3-Diene. Y. GIETL, S. VAM- HAWES, G. McKAY, E. D. KORCHINSKI, AND K. VAKAS, AND M. W. ANDERS 703 K. MIDHA 722 dmd.aspetjournals.org at ASPET Journals on September 25, 2021 Drug Metabolism and Disposition: the biological fate of chemicals

July/August 1991 Vol. 19, No. 4 CONTENTS

Changes in Pharmacokinetics of Cisplatin after Hepatic Metabolism of Azoxy Derivatives of Procarbazine by Resection in Rats. KIRSTEN SUNDBY HALL, BJ#{216}RN Aldehyde Dehydrogenase and Xanthine Oxidase. LIEN, LIV ENDRESEN, ANSTEIN BERGAN, AND HANS DONALD J. TWEEDIE, DIANA FERNANDEZ, ERIK RUGSTAD 725 MARSHALL E. SPEARMAN, RICHARD C. FELDHOFF, AND RUSSELL A. PROUGH 793 Effect of Folinic Acid on Tissue Residence and Excre- Downloaded from tion of Methotrexate in Rats. YAN-LING HE, Metabolism of Nicotine by Rat Liver Cytochromes P- YUSUKE TANIGAWARA, MASATO YASUHARA, 450: Assessment Utilizing Monoclonal Antibodies AND RYOHEI H0RI 729 to Nicotine and Cotinine. DIANNE K. HAMMOND, Disposition and Tissue Distribution of Angiopeptin in ROBERT J. BJERCKE, JOHN J. LANGONE, AND the Rat. SEEDABARUM S. CATHAPERMAL, MARIE L. HENRY W. STROBEL 804 FOEGH, CRAIG S. RAU, AND PETER W. RAMWELL 735 In Vitro Glucuronidation of 3 ‘-Azido-3 ‘-Deoxythymi- dmd.aspetjournals.org Biotransformation of Pravastatin Sodium in Humans. dine by Human Liver: Role of UDP-Glucu- DONALD W. EVERETT, THEODORE J. CHANDO, ronosyltransferase 2 Form. JEAN FRAN#{231}OIS GERALD C. DIDONATO, SAMPAT M. SINGHVI, RAJAONARISON, BRUNO LACARELLE, GEORGES

HENRY Y. PAN, AND STEPHEN H. WEINSTEIN ... 740 DE SOUSA, JACQUES CATALIN, ROGER RAHMANI 809

Stereoselective Metabolism of Carvedilol in the Rat: Species-Dependent Stereopharmacokinetics of MK- Use ofEnantiomerically Radiolabeled Pseudorace- 927, A Potent Carbonic Anhydrase Inhibitor. mates. MASAYOSHI FUJIMAKI, SHOZOU SHINTANI, JIUNN H. LIN, 1-Wu CHEN, AND TSU-HAN LIN .. 816 ANDHIDEOHAKUSUI 749 at ASPET Journals on September 25, 2021 Pharmacokinetics and Pharmacodynamics of Nifedi- Studies on the fl-Oxidation of Valproic Acid in Rat Liver Mitochondnal Preparations. SUSAN M. pine in Pregnant Sheep. C. E. NUGENT, M. HILL, BJORGE AND THOMAS A. BAILLIE 823 T. HURSEY, AND F. P. ABRAMSON 754

Aldrin Epoxidation: Catalytic Potential of Lipoxy- Enzymatic N-Methylation on Phenylzine Catalyzed by genase Coupled with Linoleic Acid Oxidation. Methyltransferases from Adrenal and Other Tis- ABHINENDER K. NAIDU, AKHILENDER K. sues. PETER H. Yu, BRUCE A. DAVIS, AND DAVE NAIDU, AND ARUN P. KULKARNI 758 A. DURDEN 830

The Disposition and Metabolism of [‘4C]Fluconazole SHORT COMMUNICATIONS in Humans. KEITH W. BRAMMER, ANTHONY J. COAKLEY, SERGE G. JEZEQUEL, AND MICHAEL H. Blood Levels of Propylene Oxide during Propylene TARBIT 764 Inhalation and Effect on Hepatic and Nasal Cyto- chrome P-450 Concentrations. KIRK R. MAPLES Application of Chemical Cytochrome P-450 Model Sys- AND ALAN R. DAHL 835 tems to Studies on Drug Metabolism: IV. Mecha- nism of Piperidine Ring Metabolism Pathways Stereoselective Sulfate Conjugation of 4-Hydroxypro- via an Iminium Intermediate. HIR05HI MASU- pranolol in Humans: Comparison of Platelet and MOTO, SHIGERU OHTA, AND MASAAKI HIROBE 768 Hepatic Activity. U. K. WALLE AND T. WALLE .. 838 Pharmacokinetics and Fate of[3H]Trospectomycin Sul- fate, a Novel Aminocyclitol Antibiotic, in Male Species Differences in the Activation of Mianserin and Female Dogs and Rabbits: Allometric Scaling to a Cytotoxic Metabolite. P. ROBERTS, N. R. with Human. D. J. NICHOLS, M. BURROWS, KITTERINGHAM, AND B. K. PARK 841 A. BYE, D. A. CONSTABLE, L. G. DRING, AND P. JEFFREY 781 Stereoselective Glucuronidation of Naproxen in Iso- lated Cells from Liver, Stomach, Intestine, and Inactivation Mechanism of Low-KM Rat Liver Mito- Colon of the Guinea Pig. MOHAMED EL MOUELHI chondrial Aldehyde Dehydrogenase by Cyanamide AND MICHAEL SCHWENK 844 in Vitro. JUAN PRUfIONOSA, MARIA LUISA SAGRISTA, AND JORGE BOZAL 787 Erratum 846

DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is an official publication of the American Society for Pharmacology and Experimental Therapeutics and is published bimonthly by Williams & Wilkins, 428 E. Preston St.. Baltimore. MD 21202-3993. Second class postage paid at Baltimore. MD and at additional mailing offices. The GST Tax Number for Canadian subscribers is 123394371. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 2 1202.3993. Price per volume: USA individual rate $75: all other countries $95 surface mail. USA institutional rate $120: all other countries $140 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Indexed by Index Medicus. Current Contents/Life Sciences. BioSciences Information Service, and Excerpia Medico. Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics. Drug Metabolism and Disposition: the biological fate of chemicals

September/October 1991 Vol. 19, No. 5 CONTENTS

The 1990 Bernard B. Brodie Award Lecture: Unique Dose Dependence in the Plasma Pharmacokinetics and Properties of the Enzymes of Detoxication. D. M. Uptake Kinetics of 2’,3’-Dideoxyinosine into ZIEGLER 847 Brain and Cerebrospinal Fluid of Rats. BARBARA L. HOESTEREY, RAYMOND E. GALINSKY, AND Stereoselective Disposition of Carprofon, Flunoxapro- BRADLEY D. ANDERSON 907 fen, and Naproxen in Rats. SEIGO IWAKAWA, Downloaded from HILDEGARD SPAHN, LESLIE Z. BENET, AND EMIL Mass Spectrometric Identification of Urinary and T. LIN 853 Plasma Metabolites of 6-(6’-Carboxyhexyl)-7- N-hexyl-l,3-diazaspiro-[4-4]-nonan-2,4-dione, a Disposition of RS-26306, a Potent Luteinizing Hor- New Cytoprotective Agent. EMILI0 BENFENATI, mone-Releasing Hormone Antagonist, in Monkeys ROBERTO FANELLI, ENRICO BOSONE, CARLO BIFFI, and Rats after Single Intravenous and Subcuta- ROBERTO CAPONI, MARINA CIANETTI, AND PAOLO neous Administration. REBECCA L. CHAN, SU C. FARINA 913 dmd.aspetjournals.org HSIEH, PETER E. HAROLDSEN, WILLIAM Ho, AND Metabolism of Cinobufagin in Rat Liver Microsomes: JOHN J. NESTOR, JR 858 Identification of Epimerized and Deacetylated Me- Excretion and Tissue Distribution of Selenium follow- tabolites by Liquid Chromatography/Mass Spec- ing Treatment of Male F344 Rats with Benzylse- trometry. LISHA ZHANG, TAKEMI YOSHIDA, lenocyanate or Sodium Selenite. OCK SOON SOHN, KIMIK0 A0KI, AND YUKIO KUROIWA 917 LEN BLACKWELL, JANICE MATHIS, WAGDY W. Identification of the Major Metabolites of the Prosta- ASAAD, BANDARU S. REDDY, AND KARAM EL-

glandin E2-Analogue Sulprostone in Human at ASPET Journals on September 25, 2021 BAYOUMY 865 Plasma, and Isolation from Urine (in Vivo) and Liver Perfusate (in Vitro) of Female Guinea-Pigs. Evidence for Oxidative Activation of Mitoxantrone in WILHELM KUHNZ, GEORG-ALEXANDER HOYER, Human, Pig, and Rat. JOACHIM BLANZ, KERSTEN SABINE BACKHUS, AND UWE JAKOBS 920 MEWES, GERHARD EHNINGER, BARBARA PROKSCH, DIETMAR WAIDELICH, BERND GREGER, AND Physiological Disposition of Alendronate, a Potent KLAUS-PETER ZELLER 871 Anti-Osteolytic Bisphosphonate in Laboratory An- imals. JIUNN H. LIN, DANIEL E. DUGGAN, 1-WU Pharmacokinetics of 2-Ethyl-l,3-hexanediol: I. Sys- CHEN, AND ROBERT L. ELLSWORTH 926 temic Disposition following Single Intravenous Doses in Male Fischer 344 Rats. STEPHEN W. Acetylator Phenotype-Dependent and -Independent FRANTZ, CHRISTINE M. GROSSE, MARILYN J. Expression of Arylamine N-Acetyltransferase Iso- TALLANT, AND BRYAN BALLANTYNE 881 zymes in Rapid and Slow Acetylator Inbred Rat Liver. DAVID W. HEIN, TIMOTHY D. RUSTAN, Stereoselective Metabolism of Felodipine in Liver Mi- KYLE D. BUCHER, WILLIAM J. MARTIN, AND ERIK crosomes from Rat, Dog, and Human. U. G. J. FURMAN 933 ERIKSSON, J. LUNDAHL, C. BAARNHIELM, AND Pharmacokinetics of lododoxorubicin in the Rat, Dog, C. 0. REGARDH 889 and Monkey. DUNCAN M. F. EDWARDS, PIETRO In Vivo Formation ofCodeinone and Morphinone from MARRARI, CONSTANTIN EFTHYMIOPOULOS, GIU- Codeine: Isolation and Identification from Guinea SEPPE BASILEO, DANIELA FRAIER, ELlo PIANEZ- Pig Bile. TAKASHI ISHIDA, MASASHI YANO, AND ZOLA, AND MARGHERITA STROLIN-BENEDETTI ... 938 SATO5HI T0KI 895 Nicotine Metabolism in Stumptailed Macaques, Ma- caca arctoides. M. SEATON, G. A. KYEREMATEN, Reactions of the Nitroso and Hydroxylamine Metabo- M. MORGAN, E. V. JESZENKA, AND E. S. VESELL 946 lites of Sulfamethoxazole with Reduced Glutathi- one: Implications for Idiosyncratic Toxicity. A Nuclear Magnetic Resonance Study of Sparteine ALASTAIR E. CRIBB, MARGARET MILLER, J. Delta Metabolite Structure. THOMAS EBNER, STEVEN LEEDER, JENNIFER HILL, AND STEPHEN P. CLAUS 0. MEESE, PETER FISCHER, AND MICHEL SPIELBERG 900 EICHELBAUM 955

DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is an official publication of the American Society for Pharmacology and Experimental Therapeutics and is published bimonthly by Williams & Wilkins. 428 E. Preston St.. Baltimore, MD 21202-3993. Second class postage paid at Baltimore. MD and at additional mailing offices. The GST Tax Number for Canadian subscribers is 123394371. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION. 428 E. Preston St., Baltimore, MD 2 1202-3993. Price per volume: USA individual rate $75: all other countries $95 surface mail. USA institutional rate $ I 20: all other countries $ 140 surface mail. Single copy $1 5 ($ 18 foreign). Prices subject to change. Indexed by Indtv .tledicus, Current Contents/Lift’ Sciences, BioSciences Information Service, and E.vcerpta Medico. Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics. Contents (cont ‘d,)

First Pass Metabolism and in Vitro Metabolism of a Determination of in Vivo Extraction Ratio from in New Orally Active Dopamine Prodrug, N-(N- Vitro Metabolism by Rat Hepatocytes. KULDEEP Acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)- SINGH, SPENCER L. TRIPP, ALAN W. DUNTON, dopamine in Dogs. M. YOSHIKAWA, S. NISHIYAMA, FRANK L. DOUGLAS, AND ASHOK RAKHIT 990 H. ENDO, Y. ToGo, AND 0. TAKAITI 960

Activation of Acetaminophen-Reactive Metabolite For- Partial Characterization of Biliary Metabolites of Pule- mation by Methylxanthines and Known Cyto- gone by Tandem Mass Spectrometry: Detection of chrome P-450 Activators. CAROLINE A. LEE, Glucuronide, Glutathione, and Glutathionyl Glu- KENNETH E. THUMMEL, THOMAS F. KALHORN, curonide Conjugates. DAVID THOMASSEN, PAUL G. SIDNEY D. NELSON, AND JOHN T. SLATTERY 966 PEARSON, JOHN T. SLATTERY, AND SIDNEY D. NELSON 997 Pharmacokinetic Analysis of the Disposition of Val- proate in Pregnant Rats. SATOSHI KOBAYASHI, Metabolism and of the Refrigerant KATSUMI TAKAI, TATSUJI IGA, AND MANABU in Vivo in Vitro Substitute 1,1,1 ,2-Tetrafluoro-2-chloroethane. MI- HANANO 972 CHAEL J. OLSON, JOHN T. JOHNSON, JOHN F. Metabolism of 3-Methylindole in Human Tissues. O’GARA, AND STEPHEN E. SURBROOK, JR 1004 WERAWAN RUANGYUTTIKARN, MARTIN L. APPLE- TON, AND GAROLD S. YOST 977 SHORT COMMUNICATION Downloaded from Effect of Congestive Heart Failure on the Intrinsic Metabolic Capacity of the Liver in the Dog. C. Product Enantioselectivity in the N-Glucosylation of LAMBERT, J. R. HALPERT, J. ROULEAU, L. JUTRAS, Amobarbital by Cats. SUZANNE E. MONGRAIN AND V. LEROYER, AND P. DU SOUICH 985 WILLIAM H. SOINE 1012 dmd.aspetjournals.org at ASPET Journals on September 25, 2021 Drug Metabolism and Disposition: the biological fate of chemicals

November/December 1991 Vol. 19, No. 6 CONTENTS

Best Paper Award for 1990 1015 Stereoselective Degradation of the Fenoprofen Acyl Glucuronide Enantiomers and Irreversible Binding Differential Effects ofProteinase K on the Components to Plasma Protein. CHRISTINE VOLLAND, HELEN ofthe Liver Microsomal Cytochrome P-450 Mixed SUN, JORG DAMMEYER, AND LESLIE Z. BENET ... 1080 Function Oxidase System. TINGLIANG SHEN, ZHENGPING ZHUANG, ROY MCCAULEY, DAVID

Renal Tubular Transport of Morphine, Morphine-6- Downloaded from PUTT, AND PAUL F. HOLLENBERG 1016 Glucuronide, and Morphine-3-Glucuronide in the Effect of Perfusion Rate on the Local Disposition of Isolated Perfused Rat Kidney. JACOBA T. VAN Cefixime in Liver Perfusion System Based on Two- CRUGTEN, BENEDETTA C. SALLUSTIO, RoGER L. NATION, AND ANDREW A. SOMOYI Compartment Dispersion Model. YOSH ITA KA 1087 YANO, KIYOSHI YAMAOKA, HIROYUKI YASUI, AND Pharmacokinetic Interaction between Verapamil and TERUMICHI NAKAGAWA 1022

Metoprolol in the Dog: Stereochemical Aspects. dmd.aspetjournals.org Identification and Structure Characterization of S-Con- SATYA S. MURTHY, WENDEE. L. NELSON, DANNY taining Metabolites of 3-Tert-butyl-4-hydroxy- D. SHEN, JOHN M. POWER, CHERYL M. CAhILL, anisole in Rat Urine and Liver Microsomes. KA- AND ALLAN J. MCLEAN 1093 ZUO TAJIMA, MARl HASHIZAKI, KENJI YAMAMOTO, AND TAMIO MIZUTANI 1028 Metabolism and Disposition of Cyclohexanone Oxime in Male F-344 Rats. DEVENDRA PARMAR AND LEO Sex Differences in the Pharmacokinetics of Recombi- T.BURKA 1101 nant Human Granulocyte Colony-Stimulating at ASPET Journals on September 25, 2021 Factor in the Rat. HIDEJI TANAKA AND TATSUHIKO Oxidation of Ethylene Glycol to Formaldehyde by Rat KANEKO 1034 Liver Microsomes: Role ofCytochrome P-450 and Reactive Oxygen Species. EWA KUKIEKA AND Cardioselectivity of a-Tocopherol Analogues, with Free ARTHURI.CEDERBAUM 1108 Radical Scavenger Activity, in the Rat. JAMES Dow, MARGARET A. PETTY, J. MARTIN GRISAR, Felbamate Pharmacokinetics in the Rat, Rabbit, and EUGENE R. WAGNER, AND KLAUS D. HAEGELE .. 1040 Dog. V. E. ADUSUMALLI, J. T. YANG, K. K. WoNG, Human Microsomal N-Oxidative Metabolism of N.KUCHARCZYK,ANDR.D.SOFIA 1116 Cocaine. STEPHEN M. ROBERTS, RAYMOND D. HARBISON, AND ROBERT C. JAMES 1046 Felbamate Metabolism in the Rat, Rabbit. and Dog. J. T. YANG, V. E. ADUSUMALLI, K. K. WONG, Age-Related Changes in Disposition and Metabolism N. KUCHARCZYK, AND R. D. SOFIA 1126 ofBenzene in Male C57BL/6N Mice. TIMOTHY F. MCMAHON AND LINDA S. BIRNBAUM 1052 Felbamate in Jitro Metabolism by Rat Liver Micro- somes. V. E. ADUSUMALLI, K. K. WON;, N. Elimination of the Antiviral Drug 5-Ethyl-2’-deoxy- KUCIIARCZYK. AND R. D. SOFIA 1135 uridine by the Isolated Perfused Rat Liver. JAMES M. JOLY AND WALTER M. WILLIAMS 1058 The Disposition and Metabolism of [‘4C]Piritrexim in Metabolism and Disposition of Diethylene Glycol in Dogs after Intravenous and Oral Administration. Rat and Dog. JAMES M. MATHEWS, MICHAEL K. JOSEPH L. WOOLI.EY, DIANE V. DEANGELIS, PARKER, AND HAZEL B. MATTHEWS 1066 MICHAEL E. GRACE, SAM H. T. LIAO, RONALD C. CROUCH, AND CARL W. SIGEL 1139 Human Liver Arylamine N-Sulfotransferase Activity: Thermostable Phenol Sulfotransferase Catalyzes Tissue Distribution and in Jis’o Immunosuppressive the N-Sulfation of 2-Naphthylamine. J. SERGIO Activity of Liposomal Cyclosporine. KIUMARS VA- HERNANDEZ, STEPHEN P. POWERS, AND RICHARD DIEI, GABRIEL LOPEZ-BERESTFIN, ROMAN PEREZ- M. WEINSHILBOUM 1071 SOLER,ANDDAVIDR. LUKE 1147

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DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is an official publication of the American Society for Pharmacology and Experimental Therapeutics and is published bimonthly beginning in January by Williams & Wilkins. 428 E. Preston St.. Baltimore. MD 21202-3993. Second class postage paid at Baltimore. MD and at additional mailing offices. The GST Tax Number for Canadian subscribers is I 2339437 1. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION. 428 E. Preston St., Baltimore. MD 21202-3993. Price per volume: USA individual rate $80: all other countries $100 surface mail. USA institutional rate $ 130: all other countries $ I 50 surface mail. Single copy S I 5 ($ 18 foreign). Prices subject to change. Indexed by Indt’v .tledicus. Current Contents/Lilt’ Sciences. BioSciences Information Service, and Llvcerpta .tfedica. Copyright c 1991 by the American Society for Pharmacology and Experimental Therapeutics. Contents (coil! ‘d.)

Characterization of a Rat Liver Glucuronosyltrans- Microsomal Hydroxylation of Triallate: Identification ferase that Glucuronidates the Selective Dl Antag- of a 2-Chloroacrylate Glutathione Conjugate onist, SCH 23390, and Other Benzazepines. CLARK Using Heteronuclear Multiple Quantum Coher- E. TFDFORD, VILMA B. RUPERTO, AND ALLEN ence NMR Spectroscopy. AMY G. HACKETT, JOHN BARNETT 1152 J. KOTYK, HIDEJI FUJIWARA. AND EUGENE W. LOGUSCH 1163 SHORT COMMUNICATIONS

Synthesis and Identification of a Novel Tetrazole Me- Erratum 1165 tabolite of the Angiotensin II Receptor Antagonist DuP 753. RALPH A. STEARNS, GEORGE A. Doss, Author Index 1167 RANDALL R. MILLER, ANt) SHUET-HING LEE CHIU 1160 Subject Index 1170 Downloaded from dmd.aspetjournals.org at ASPET Journals on September 25, 2021