Drug Metabolism and DIsposition: the biological fate of chemicals

January/February 1990 Vol. 18, No. 1 CONTENTS

Pharmacokinetics and Metabolism ofthe Pharmacolog- Not Accompanied by S-Nitrosothiol Production. ically Active 4’-Hydroxylated Metabolite of Pro- S. CHONG AND HO-LEUNG FONG 61 pranolol in the Dog. D. D. CHRIST, U. K. WALLE, J. E. OATIS, JR., AND T. WALLE Isolation and Identification of a Novel Human Metab- olite of Cyclosponn A: Dihydro-CsA M 17. G. PA- Metabolism of Chloronitrobenzenes by Isolated Rat TRICK MEIER, SANG B. PARK, DENNY J. GMUR, Hepatocytes. DOUGLAS E. RICKERT AND SARA D. AND GARY C. YEE 68 HELD S Phenytoin Disposition in the Pregnant Rat: Dose-de- Downloaded from Effect of Microsomal Enzyme Inducers on Biliary and pendent Studies and Salicylate Effects. PATRICIA Urinary Excretion of Acetaminophen Metabolites CLEVELAND AND CLARENCE T. UEDA 72 in Rats: Decreased Hepatobiliary and Increased Hepatovascular Transport of Acetaminophen-glu- A Reversible Clearance Model for the Enterohepatic curonide after Microsomal Enzyme Induction. Circulation of Drug and Conjugate Metabolite Pair. ROBIN L. 0. SEMMES AND DANNY D. SHEN . 80 ZOLTAN GREGUS, CHERUKURY MADHU, AND CUR- dmd.aspetjournals.org TIS D. KLAASSEN 10 Disposition ofEthimizol, a Xanthine-related Nootropic Drug, in Perfused Rat Liver and Isolated Hepato- Comparative Studies of the In Vitro Metabolism and Covalent Binding of ‘4C-Benzene by Liver Slices cytes. STEFAN BEZEK, MARIAN KUKAN, ZOLTAN KALLAY, ToMA TRNOVEC, MILAN STEFEK, AND and Microsomal Fraction of Mouse, Rat, and Hu- LEVON B. PI0TR0vSKIY man. JOANNE I. BRODFUEHRER AND GARTH 88 Powis 20 The Effect of Enzyme Induction and Inhibition on the Structural Characterization of Urinary Metabolites of Disposition of the Xanthine-related Nootropic at ASPET Journals on September 23, 2021 the Antiarrhythmic Drug Encainide in Human Drug Ethimizol in Perfused Liver and Hepatocyte Subjects. HEMANT K. JA.JOO, ROBERT F. MAYOL, of Rats. MARIAN KUKAN, STEFAN BEZEK, MILAN JOHN LABUDDE, AND IAN A. BLAIR 28 STEFEK, ToMA TRNOVEC, MARIA DURIOVA, AND LEVON PIOTROVISKIY 96 Azoreduction of Dimethylaminobenzene (DAB) in Pn- mary Cultures of Rat Hepatocytes: Effect of Hy- Placental Transfer, Tissue Distribution, and Pharma- cokinetics of Cyclosporine in the Pregnant Rabbit. polipidemic Agents. ALBERT M. STODDART AND WALTER G. LEVINE 36 LORENZO SANGALLI, ANGELA BORTOLOTTI, FLAVIO PASSERINI, AND MAURIzI0 BONATI 102 Pharmacokinetics of Disopyramide in the Dog: Impor- tance of Mono-N-dealkylated Metabolite Kinetics Metabolism of Prostaglandin F2. in Sheep. VLADIMIR in Assessing Pharmacokinetic Modeling of the Par- DIM0v AND KRISTER GREEN 107 ent Drug. CHYUNG S. COOK, PETER R. GUILT, KEN The Metabolism and Disposition of ‘4C-Fenofibrate in KOWALSKI, SAMIR GUPTA, JAMES OPPERMANN, Human Volunteers. ANDRE WElL, JOHN CALD- AND Aziz KARIM 42 WELL, AND MARGHERITA STROLIN-BENEDETFI ... 115

Purification and Characterization of Human Kidney Drug Interaction: Effects of Salicylate on Pharmacoki- Cytosolic Cysteine Conjugate 3-Lyase Activity. netics of Valproic Acid in Rats. H5IU-YING Yu, LAWRENCE H. LASH, RITA M. NELSON, RUSSELL YU-ZEN SHEN, YUICHI SUGIYAMA, AND MANABU A. VAN DYKE, AND M. W. ANDERS 50 HANANO 121 Pharmacokinetics of Prednisolone and Its Local Anti- inflammatory Steroid-21-oate Ester Derivatives: In Vitro and In Vivo Comparative Study. SAYED M. SHORT COMMUNICATION H. AL-HABET, IRACH B. TARAPOREWALA, AND HENRY J. LEE 55 Pharmacokinetic Interaction Between Ethanol and Ni- trendipine in the Rat: Role of Hypothermia as a Thiol-mediated Catalysis of Nitroglycerin Degradation Contributing Mechanism. KATHLEEN M. BOJE AND by Serum Proteins: Increase in Metabolism Was HO-LEUNG FUNG 127

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 $70; Japan $107 (includes air freight); all other countries $85 surface mail. USA institutional rate $110; Japan $147 (includes air freight); all other countries $125 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics. Drug Metabolism and DIsposition: the biological fate of chemicals

March/April 1990 Vol. 18, No. 2 CONTENTS

Role of P-450c in the Formation of a Reactive Inter- olism and Pharmacologic Activity of Flurazepam. mediate of Chiorotrianisene (TACE) by Hepatic S. CAPELLO, L. HENDERSON, F. DEGRAZIA, D. Microsomes from Methylcholanthrene-treated rats. LIBERATO, W. GARLAND, AND C. TOWN 190 MARLENE J. JUEDES AND DAVID KUPFER 131 Determination of Hepatic Blood Flow in the Rat Using Metabolic Disposition Studies on Simvastatin, a Sequential Infusions of Indocyanine Green or Ga- Cholesterol-lowering Prodrug. S. VICKERS, C. A. lactose. GARY M. POLLACK, KIM L. R. BROUWER, Downloaded from DUNCAN, 1-Wu CHEN, A. ROSEGAY, AND D. E. KARENB.DEMBY.ANDJAMIA.JONES 197 DUGGAN 138 Biotransformation of Lovastatin. I. Structure Elucida- Metabolism of Temelastine (SK&F 93944) in Hepato- tion ofln Vitro and In Vivo Metabolites in the Rat cytes from Rat, Dog, Cynomolgus Monkey, and and Mouse. KAMLESH P. VYAS, PRASAD H. KARl, Man. H. G. OLDHAM, P. STANDRING, S. J. NoR- STEVEN M. PITZENBERGER, RITA A. HALPIN,

MAN, T. J. BLAKE, I. BEATTIE, P. J. Cox, AND R. J. dmd.aspetjournals.org HARRI G. RAMJIT, BYRON ARISON, JOAN S. MUR- CHENERY 146 PHY, WILLIAM F. HOFFMAN, MICHAEL S. Disposition in Animals of a New Anti-HIV Agent: SCHWARTZ, EDGAR H. ULM, AND DANIEL E. 2’,3’-Didehydro-3’-Deoxythymidine. JOHN W. DUGGAN 203 RUSSELL, VALERIE J. WHITEROCK, DIANA MAR- RERO, AND LEWIS J. KLUNK 153 Disposition ofa New Orally Active Dopamine Prodrug, N-(N-Acetyl-L-methionyl)O,O-bis-(ethoxycarbonyl)- Bioavailability Assessment of Cyclosporine in the Rat: dopamine (TA-870) in Humans. M. YOSHIKAWA,

Influence of Route of Administration. DAVID R. H. ENio, K. KOMATSU, M. FUJIHARA, 0. TAKAITI, at ASPET Journals on September 23, 2021

LUKE. LANE J. BRUNNER, AND KIUMARS VADIEI . 158 T. KAGOSHIMA, M. UMEHARA, AND H. ISHIKAWA 212

Bioalkylation of Benz[a]Anthracene as a Biochemical Biotransformation of Lovastatin. II. In Vitro Metabo- Probe for Carcinogenic Activity: Lack of Bioalky- lism by Rat and Mouse Liver Microsomes and laton in a Series of Six Noncarcinogenic Polynu- Involvement ofCytochrome P-450 in Dehydrogen- clear Aromatic Hydrocarbons. JAMES W. FLESHER ation ofLovastatin. KAMLESH P. VYAS, PRASAD H. AND STEVEN R. MYERS 163 KARl, SHIMOGA R. PRAKASH, AND DANIEL E. Selective Inactivation by Chlorofluoroacetamides of the DUGGAN 218 Major Phenobarbital-inducible Form(s) of Rat The Effect of Aspartame on the Activity of Rat Liver Liver Cytochrome P-450. JAMES HALPERT, JOHN- Xenobiotic-metabolizing Enzymes. V. A. TUTE- YAN JAW, CELIA BALFOUR, AND LAURENCE S. LYAN, L. V. KRAVCHENKO, AND E. E. KUZMINA ... 223 KAMINSKY 168

Distribution and Metabolism of the Retinoid, N-(4- Pharmacokinetics and Biotransformation of the Cyclo- Methoxyphenyl)-all-trans-retinamide, the Major sporine Metabolite M- 17 in the Rabbit. KENNETH Metabolite of N-(4-Hydroxyphenyl)-all-trans-retin- COPELAND, MICHAEL LUKOWSKI, RANDALL amide, in Female Mice. THERESA A. HULTIN, YATSCOFF, JAMES THLIVERIS, AND NICHOLAS MARK S. FILLA, AND DAVID L. MCCORMICK 175 HONCHARIK 226

Metabolite Inhibition of Parent Drug Biotransforma- Clearance of Prednisone in Isolated Perfused Livers of tion: Studies of Diltiazem. S-C. TSAO, T. H. DICK- Normal and Uremic Rats: Effects of Acute and INSON, AND D. R. ABERNETHY 180 Chronic Cyclosporine A Administration. MARTIN In Vivo Metabolism of Isomeric Naphthalene Oxide EGFJORD, HENRIK DAUGAARD, AND KLAUS OLGAARD 231 Glutathione Conjugates. MICHAEL BUONARATI, A. DANIEL JONES, AND ALAN BUCKPITT 183 The Disposition of Valpromide in Rats and the Isolated The Effect of the Cytochrome P-450 Suicide Inactiva- Perfused Rat Liver. HANNA BILLIG, EHUD ZIV, tor, l-Aminobenzotriazole, on the In Vivo Metab- HANOCH BAR-ON, AND MEIR BIALER 238

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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. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION. 428 E. Preston St.. Baltimore. MD 21202-3993. Price per volume: USA individual rate $70: Japan $107 (includes air freight): all other countries $85 surface mail. USA institutional rate $110: Japan $147 (includes air freight): all other countries $125 surface mail. Single copy $15 ($ 18 foreign). Prices subject to change. Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics. Contents (con! ‘ci.)

Physiologically Based Pharmacokinetics of a New Pe- Effect of Rat Tissue Volume on the Distribution Ki- nem, SUNS 555, for Evaluation of In Vivo Efficacy. netics of Biperiden as a Function of Age in Rats. AKIRA TSUJI, HITOSHI SATO, IKUMI TAMAI, HIDEKI KOICHI YOKOGAWA, EMI NAKASHIMA, AND FUJIO ADACHI, TATSURO NISHIHARA, MASAJI ISHIGURO, ICHIMURA 258 NoRlo OHNUMA, AND TERUHISA NOGUCHI 245

Relative Contribution of the Gut, Liver, and Lung to the First-Pass Hydrolysis of Orally Administered Enzymatic Reduction of an Epoxysuccinic Acid Deriv- ‘4C-Fosinopril Sodium in Dogs: In Vivo and In ative by Rat Cecal Microflora. KIYOMI FUKUSHIMA, Vitro Studies. R. A. MORRISON, S. M. SINGHVI, A. MASAYUKI ARAI, ToSHlo SUWA, AND TETSUO E. PETERSON, D. A. PoCrnl, AND B. H. MIGDALOF 253 SATOH 264 Downloaded from dmd.aspetjournals.org at ASPET Journals on September 23, 2021 Drug Metabolism and Disposition: the biological fate of chemicals

May/June 1990 Vol. 18, No. 3 CONTENTS

LE1TERS TO THE EDITOR Tissue Distribution and Metabolic Disposition of Zi- dovudine in Rats. PAULO DE MIRANDA, THIMYSTA The Role of Sulfate Conjugation in the Elimination C. BURNETrE, AND STEVEN S. GOOD 315 Kinetics of Diflunisal in the Rat. R. VERBEECK .. 267 Isolation and Characterization of an Ether Glucuronide Response to Letter to the Editor, “Diflunisal, A Unique Model Compound for Ester and Ether Glucuroni- of Zidovudine, a Major Metabolite in Monkeys and Humans. STEVEN S. GooD, CECILIA S. KOBLE, Downloaded from dation”. JIUNN H. LIN 268 RONALD CROUCH, ROBERT L. JOHNSON, JANET L. RIDEOUT, AND PAULO DE MIRANDA 321 COMMENTARY Effect of Growth Hormone on Caffeine Metabolism in The Effect of Hepatic Blood Flow on Formation of Hypophysectomized Rats. THIERRY BIENVENU, Metabolites. K. SANDY PANG AND GERARD J. GERARD PONS, ELISABETH REY, MARIE-ODILE MULDER 270

RICHARD, PHILIPPE D’ATHIS, MAURICE J. ARNAUD, dmd.aspetjournals.org Ethyl Carbamate Metabolism: In Vivo Inhibitors and AND GEORGES OLIVE 327 In Vitro Enzymatic Systems. TOSHINORI YAMA- Pathways of Gallopamil Metabolism: Regiochemistry MOTO, WILLIAM M. PIERCE, JR., HARREL E. HURST, and Enantioselectivity of the N-Dealkylation Proc- Dl CHEN, AND WILLIAM J. WADDELL 276 esses. ABDUL E. MUTLIB AND WENDEL L. Pharmacokinetics and Disposition of WR-l065 in the NELSON 331 Rhesus Monkey. MANGOLD, HUELLE, D. J. B. K. Pharmacokinetics of Methysergide and Its Metabolite M. A. MILLER, R. S. GEARY, D. 0. T. SANCHEZ- Methylergometrine in the Rat. U. BREDBERG AND at ASPET Journals on September 23, 2021 BARONA, N. F. SWYNNERTON, L. FLECKSTEIN, AND L. PAALZOW 338 T. M. LUDDEN 281 The Hydrolysis-Activation of the Adriamycin Cardi- Inhibition of Leucine Enkephalin Metabolism in Rat oprotective Agent ICRF- 187 ((+)- 1,2-Bis(3,5-diox- Blood, Plasma, and Tissues In Vitro by an Ami- opiperazinyl-l-yl)propane). BRIAN HASINOFF .... 344 noboronic Acid Derivative. MUNIR A. HUSSAIN, SUSAN M. ROWE, ASHOK B. SHENVI, AND BRUCE Oxidative Cleavage of the Pentyl Side-Chain of Can- J. AUNGST 288 nabinoids: Identification of New Biotransforma- tion Pathways in the Metabolism of 4’-Hydroxy- Nitroglycerin Metabolism in Subcellular Fractions of \9-Tetrahydrocannabinol in the Mouse. D. J. Rabbit Liver: Dose Dependency of Glyceryl Dini- HARVEY 350 trate Formation and Possible Involvement of Mul- tiple Isozymes of Glutathione S-Transferases. Tolbutamide Hydroxylation by Human, Rabbit, and DAVID T.-W. LAU AND LESLIE Z. BENET 292 Rat Liver Microsomes and By Purified Forms of Cytochrome P-450. MAURICE E. VERONESE, MI- Inhibition and Induction of Theophylline Metabolism CHAEL E. MCMANUS, PISAMAI LAUPATTARAKASEM, by 8-Methoxypsoralen: In Vivo Study in Rats and JOHN 0. MINERS, AND DONALD J. BIRKETr 356 Humans. GLEN APSELOFF, DALE R. SHEPARD, MARK A. CHAMBERS, SOPONE NAWOOT, DENNIS Mexiletine Metabolism In Vitro by Human Liver. F. C. MAYS, AND NICHOLAS GERBER 298 BROLY, C. LIBERSA, AND M. LHERMITTE 362

Bromobenzene Metabolism In Vivo and In Vitro: The Glucuronidation of 3’-Azido-3’-Deoxythymidine by Mechanism of 4-Bromocatechol Formation. NA- Rat and Human Microsomes. ERIKA M. CRETFON, TALIE E. MILLER, DAVID THOMAS, AND RUTH E. D. VINCENT WATERHOUS, RAE BEVAN, AND JEAN- BILLINGS 304 PIERRE SOMMADOSSI 369

Pathways of Gallopamil Metabolism: Regiochemistry Metabolism of Alachlor by Rat and Mouse Liver and and Enantioselectivity of the O-Demethylation Nasal Turbinate Tissues. PAUL C. C. FENG, ALAN Processes. ABDUL E. MUTLIB AND WENDEL L. G. WILSON, ROBERT H. MCCLANAHAN, JAMES E. NELSON 309 PATANELLA, AND STEPHEN J. WRATTEN 373

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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. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 21202-3993. Price per volume: USA individual rate $70; Japan $107 (includes air freight): all other countries $85 surface mail. USA institutional rate $1 10; Japan $147 (includes air freight); all other countries $125 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics. Contents (cont’d)

The Effect of Primary Metabolites of the Xanthine- Xenobiotics and Comparison with the Enzymes Related Nootropic Drug Ethimizol on Its Hepatic Purified from Liver. TOSHIFUMI AOYAMA, KEN- Extraction Ratio. MARIAN KUKAN, STEFAN BEZEK, NETH KORZEKWA, TAMIHIDE MATSUNAGA, Ki- TOMAS TRNOVEC, AND LEVON B. PIOTROVSKIY... 378 YOSHI NAGATA, JAMES GILLETTE, HARRY Y. GEL- BOIN, AND FRANK J. GONZALEZ 383 SHORT COMMUNICATION cDNA-Directed Expression of Rat P450s IIA1 and IIA2: Catalytic Activities Toward Steroids and Erratum 386 Downloaded from dmd.aspetjournals.org at ASPET Journals on September 23, 2021 Drug Metabolism and DIsposition: the biological fate of chemicals

July/August 1990 Vol. 18, No. 4 CONTENTS

Letter to the Editor and Response 387 JOSEPH A. HRABIE, LENA OHANNESIAN, YOUNG- HUN HEUR, BRUCE A. MIC0, AND LARRY K. Interspecies Differences in Stereoselective Protein Bind- KEEFER 447 ing and Clearance of MK-57 1. D. J. T0CC0, F. A. DELUNA, A. E. W. DUNCAN, J. H. HSIEH, AND J. N-Depyridination and N-Dedimethylaminoethylation H.LIN 388 ofTripelennamine and Pyrilamine in the Rat: New Downloaded from Metabolic Pathways. S. Y. YEH 453 Comparison of the Interactions of Pyrazole and its Metabolite 4-Hydroxypyrazole with Rat Liver Mi- Stimulation Mechanism of Guinea Pig Liver-mediated crosomes. LIVIU A. CLEJAN AND ARTHUR I. Reduction of Naloxone by Morphine. YoSHrro CEDERBAUM 393 KUMAGAI, TAKASHI TODAKA, SHIGERU YAMANO, AND SATOSHI T0KI 462 Tissue, Species, and Substrate Concentration Differ-

ences in the Position-selective Hydroxylation of N- Effect of Recombinant Human Interleukin-1f3 and Tu- dmd.aspetjournals.org Nitrosodibutylamine: Relationship to the Distri- mor Necrosis Factor a on Liver Cytochrome P- bution of Cytochrome P-450 Isozymes 2 (IIB) and 450 and Serum a-l-Acid Glycoprotein Concentra- S (IVB). JOHANNES SCHULZE, ELMAR RICHTER, tions in the Rat. CHRISTIAN PoUs, JEAN-PAUL GI- AND RICHARD M. PHILPOT 398 ROUD, CHANTAL DAMAIS, DENIS RAICHVARG, AND LAURENCE CHAUVELOT-MOACHON 467 Effects of Thyroid Dysfunction on Prednisolone and Prednisone Interconversion and Disposition in the The Pharmacokinetics of Etodolac Enantiomers in the Rat. RYO MURATA, DAVID B. HAUGHEY, AND WIL- Rat: Lack of Pharmacokinetic Interaction Between at ASPET Journals on September 23, 2021 LIAM J. JUSKO 403 Enantiomers. DI0N R. BROCKS AND FAKHREDDIN JAMALI 471 Metabolic Fate ofAlclometasone Dipropionate in Rats, Rabbits, and Mice: Metabolic Products and Path- In Vitro and In Vivo Biotransformation of Simvastatin, way Following Subcutaneous Administration. S. an Inhibitor of HMG CoA Reductase. S. VICKERS, AOYAMA AND K. KAMATA 409 C. A. DUNCAN, K. P. VYAS, H. P. KARl, B. ARISON, S. R. PRAKASH, H. G. RAMJIT, S. M. PITZENBER- The Role ofCytochromes P-450 and Flavin-containing GER, G. STOKKER, AND D. E. DUGGAN 476 Monooxygenase in the Metabolism of(S)-Nicotine by Rabbit Lung. DAVID E. WILLIAMS, MARK K. Species-dependent Enantioselective Plasma Protein SHIGENAGA, AND NEAL CASTAGNOLI, JR 418 Binding of MK-57 1, a Potent Leukotriene D4 An- tagonist. JIUNN H. LIN, FLORENCIA A. DELUNA, A Pharmacokinetic Model for Isosorbidedinitrate, Iso- EDGAR H. ULM, AND DOMINICK J. TOCCO 484 sorbide-2-mononitrate, and Isosorbide-S-mononi- trate. D. SMITH, W. ALDRICH, M. DEY, R. ENEVER, Structural Determination of the Conjugated Metabo- R. WARNER, AND R. WEIERSTALL 429 lites of Ritodrine. WAYNE T. BRASHEAR, BETTY R. KUHNERT, AND ROBERT WEI 488 Interspecies Comparison of the Pharmacokinetics of Aldose Reductase Inhibitors. R. K. BRAZZELL, Y. Effects of Age and Dose on Disposition and Metabolism H. PARK, C. B. WOOLDRIDGE, B. MCCUE, R. BAR- of Salicylic Acid in Male Fischer 344 Rats. TIMO- KER, R. COUCH, AND B. YORK 435 THY F. MCMAHON, JANET J. DILIBERTO, AND LINDA S. BIRNBAUM 494 Metabolism and Disposition of Clarithromycin in Man. J. L. FERRERO, B. A. Bopp, K. C. MARSH, S. C. Inhibition of the Metabolism of Ethyl Carbamate by QUIGLEY, M. J. JOHNSON, D. J. ANDERSON, J. E. Acetaldehyde. NORIMITSU KURATA, RAY KEMPER,

LAMM, K. G. TOLMAN, S. W. SANDERS, J. H. HARRELL E. HURST, AND WILLIAM J. WADDELL . 504 CAVANAUGH, AND R. C. SONDERS 441 Radioimmunoassay of Nicotine-i’ ‘#{176}-Iminium Ion, an Deuterium Isotope Effect on the Toxicokinetics of Intermediate Formed During the Metabolism of Monomethylamine in the Rat. ANTHONY J. STREE- Nicotine to Cotinine. R. SCOTT OBACH AND HELEN TER, RAYMOND W. NIM5, PAMELA R. SHEFFELS, VAN VUNAKIS 508

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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. POSTMASTER: Send address changes to DRUG METABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 21202-3993. Price per volume: USA individual rate $70; Japan $107 (includes air freight); all other countries $85 surface mail. USA institutional rate $110; Japan $147 (includes air freight); all other countries $125 surface mail. Single copy $15 ($18 foreign). Prices subject to change. Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics. Contents (cont’d)

Biotransformation of Halothane in Guinea Pig Liver SHORT COMMUNICATIONS Slices. H. N. GHANTOUS, J. FERNANDO, A. J. GON- DOLFI, AND K. BRENDEL 514 Unsubstituted Amides: New Class of Potent Inhibitors of Human Microsomal Epoxide Hydrolase. BRAD- Effects of Vanadate on Hepatic Cytochrome P-450 LEY M. KERR AND REN#{201}H. LEVY 540 Expression in Streptozotocin-diabetic Rats. B. S. Effects of Carbon Tetrachlorde Administration to DONAHUE AND E. T. MORGAN 519 Guinea Pigs on Cytochromes P-450 and Antioxi- dant Levels in the Inner and Outer Zones of the Studies on the Metabolism and Chiral Inversion of Adrenal Cortex. D. A. STAATS, D. P. LOHR, AND Ibuprofen in Isolated Rat Hepatocytes. SUSAN M. H. D. COLBY 543 SANIN5, WADE J. ADAMS, DAVID G. KAISER, GOR- DON W. HALSTEAD, AND THOMAS A. BAILLIE.... 527 Isolation and Characterization of an Unusual Glucu- ronide Conjugate of Rimantadine. S. Y. BROWN, W. A. GARLAND, AND E. K. FUKUDA 546 Morphologic Changes and Covalent Binding of 1,1- Dichloorethylene in Clara and Alveolar Type II Microsomal Metabolism of the 1“,l”-Dimethylheptyl Cells Isolated from Lungs of Mice Following In Analogue of Cannabidiol: Relative Percent of Mo- Vivo Administration. P. G. FORKERT, B. A. nohydroxy Metabolites in Four Species. E. SA-

GEDDES, D. W. BIRCH, AND T. E. MASSEY 534 MARA, N. K. BROWN, AND D. J. HARVEY 548 Downloaded from dmd.aspetjournals.org at ASPET Journals on September 23, 2021 Drug Metabolism and DisposItion: the biological fate of chemicals

September/October 1990 Vol. 18, No. 5 CONTENTS

Letter to the Editor: Expressing the Specificity and the guanidine in Animals. DAVID G. WALKER, MI- Potency of Cytochrome P-450 Inducers Toward CHAEL HUTCHISON, TERESA A. SHEPARD, PETER M. 7-Ethoxyresorufin. MORENO PAOLINI, GI0RGI0 OSBORNE, SUSAN M. ALLENBY, ANDREW J. WEBB, CANTELLI FORTI, AND CARLO BAUER 551 NICHOLAS J. VINEY, MARTIN A. PUE, RICHARD J. CHENERY, PHILLIPA J. WooD, AND DEREK A. Response S. J. GLASS AND R. B. L. VAN LIER 551 ROSS 613 Downloaded from

Bioavailability, Metabolism, and Renal Excretion of Absorption of a Novel Prodrug of L-DOPA, I.-3-(3- Benzoic Acid in the Channel Catfish (Icialurus Hydroxy-4-pivaloyloxyphenyl)alanine (NB-355): Punctatus). STEVEN M. PLAKAS AND MARGARET In Vitro and In Situ Studies. AKIEIIRO HISAKA, 0. JAMES 552 SATOE KASAMATSU, NORIHIR0 TAKENAGA, AND MASAKATSU OHTAWA 621 Isozymes of Cytochrome P-450 that Metabolize Naph-

thalene in Liver and Lung of Untreated Mice. The Formation, Disposition, and Hepatic Metabolism dmd.aspetjournals.org KIY0SHI NAGATA, BRIAN M. MARTIN, JAMES R. of Dimethylnitrosamine in the Pig. G. W. HAR- GILLETTE, AND HENRY A. SASAME 557 RINGTON, P. N. MAGEE, H. M. PYLYPIW, JR., R. Effect of Diabetes on Disposition and Renal Handling KOZENIAUSKAS, R. F. BEVILL, D. R. NELSON, ANI) J. C. TI-IURMON 626 of Cefa.zolin in Rats. MASAYUKI NADAI, HIDEO YOSHIZUMI, TAKAFUMI KUZUYA, TAKAAKI HASE- Thiopurine Methyltransferase Isozymes in Human GAWA, IKUO JOHNO, AND SHIKIFUMI KITAZAWA . 565 Renal Tissue. JON A. VAN LOON AND RICHARD M.

Identification of Urinary Metabolites of Cannabidiol WEINSHILBOUM 632 at ASPET Journals on September 23, 2021 in the Dog. E. SAMARA, M. BIALER, AND D. H. Covalent Binding of Zomepirac Glucuronide to Pro- HARVEY 571 teins: Evidence for a Schiff Base Mechanism. First-Pass Metabolism of Gentisamide: Influence of PHILIP C. SMITH, LESLIE Z. BENET, AND ANTONY Intestinal Metabolism on Hepatic Formation of F. MCDONAGH 639 Conjugates. Studies in the Once-Through Vascu- Identification and Distribution in the Rat of Acidic larly Perfused Rat Intestine-Liver Preparation. Metabolites ofTamoxifen. PETER C. RUENITZ AND HIROKI HIRAYAMA AND K. SANDY PANG 580 NITIN T. NANAVATI 645

Estimations of Intestinal and Liver First-Pass Metabo- Pretranslational Suppression of Cytochrome P-450h lism In Vivo: Studies on Gentisamide Conjugation (IIC 1 1) Gene Expression in Rat Liver after Admin- in the Rat. HIR0KI HIRAYAMA, JOHN MORGADO, istration of Interferon Inducers. EDWARD T. MOR- IZABELLA GASINSKA, AND K. SANDY PANG 588 GAN AND CATHERINE A. NORMAN 649

Cyclosporin A Drug Interactions: Screening for Induc- Pharmacokinetics of the Anti-AIDS Drug 2’,3’-Di- ers and Inhibitors of Cytochrome P-450 (Cyclo- deoxyinosine (NSC 612049) in the Rat. GENE sporin A Oxidase) in Primary Cultures of Human F. RAY, WILLIAM D. MASON, ANI) MOSTAFA Z. Hepatocytes and in Liver Microsomes. LYDIANE BADR 654 PICHARD, ISABELLE FABRE, GERARD FABRE, JACQUES DOMERGUE, BERNARD SAINT AUBERT, Metabolism and Cytotoxicity of Acetaminophen in He- GEORGES MOURAD, AND PATRICK MAUREL 595 patocyte Cultures From Rat, Rabbit, Dog, and Monkey. TERESA A. SMOLAREK, CATHERINE V. In Vitro Metabolism of the Novel Anti-inflamma- HIGGINS, AND DAVID E. AMACHER 659 tory Agent 6-(4’-Fluorophenyl)-S-(4’-pyridyl) -2,-dihydroimidazo-2,lb-thiazole. M. 0. HOW- Metabolism of the Carcinogen 3-Methylcholanthrene ARD, J. F. NEWTON, D. J. KEOHANE, L. P. Y0DIS, in Human Bone Marrow Preparations. STEVEN R. C. M. SAVERINO, C. W. QUALLS, JR., AND L. W. MYERS AND JAMES W. FLESHER 664 SCHWARTZ 607 Pharmacokinetics of Codeine After Parenteral and Oral The Disposition of 2-Cyano-l-methyl 3-(4-(4-methyl- Dosing in the Rat. JAYMIN SHAH AND WILI.IAM D. 6-oxo- 1,4,S,6-tetrahydro-pyridazin-3-yl)phenyl)- MASON 670 (‘ontinued 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 21202-3993. 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 $70: Japan $107 (includes air freight): all other countries $85 surface mail. USA institutional rate $1 10: Japan $147 (includes air freight): all other countries $all other countries $125 surface mail. Single copy $15 ($ 18 foreign). Prices subject to change. Copyright (© 1990 by the American Society for Pharmacology and Experimental Therapeutics. Contents (cont ‘d)

Pharmacokinetics of a Novel Butylated Hydroxy- mans. J. A. SCATINA, D. S. WELLS, H. B. KIMMEL, toluene-Thiazolidinone CNS Antiischemic Agent C. J. KEMPER, AND S. F. SISENWINE 746 LY256548 in Rats, Mice, Dogs, and Monkeys. K. J. Ruterbories and T. D. Lindstrom 674 Metabolism of 2-Chloro-1, 1-difluoroethane to Glyox- ylic and Glycolic Acid in Rat Hepatic Microsomes. Acetylator Genotype-dependent Expression of Arylam- MAX T. BAKER, MARIA T. VASQUEZ, JAMES N. me N-Acetyltransferase and N-Hydroxyarylamine BATES, AND CHAO-KUO CHIANG 753 O-Acetyltransferase in Syrian Inbred Hamster Intestine and Colon: Identity with the Hepatic Interaction of Continine with Rat Hepatic Microsomal P-450: Comparison with Metyrapone and Immu- Acetylation Polymorphism. FREDRICK OGOLLA, nomodulation ofContinine and Metyrapone Bind- RONALD J. FERGUSON, WARD G. KIRLIN, ALMA ing by Monoclonal Anti-continine Antibodies. TRINIDAD, ALLEN F. ANDREWS, MANDI MPEZO, ROBERT J. BJERCKE, DIANNE K. HAMMOND, AND DAVID W. HEIN 680 HENRY W. STROBEL, AND JOHN J. LANGONE . ... 759 Stereochemical Differences in the Metabolism of 3,4- Hepatic Protein Arylation, Glutathione Depletion, and Methylenedioxymethamphetamine In Vito and In Metabolite Profiles of Acetaminophen and a Non- Vitro: A Pharmacokinetic Analysis. ARTHUR K. CHO, MASAYUKI HIRAMATSU, EMMA W. DIsTE- hepatotoxic Regioisomer. 3 ‘ -Hydroxyacetanelide, in the Mouse. MOHAMED S. RASHED, TIMOTHY G. FANO, ANN S. CHANG, AND DONALD J. JENDEN.. 686 MYERS, AND SIDNEY D. NELSON 765 Downloaded from Glucuronidation of 2-Arylpropionic Acids Pirprofen, Flurbiprofen, and Ibuprofen by Liver Microsomes. Metabolism of 1 , l-Dichloro-cis-diphenylcyclopropane by Rat Liver Microsomes. 0. CAPUTO, G. GROSA, J. MAGDALOU, V. CHAGES, C. LAFAURIE, AND G. M. CERUTI, F. ROCCO, AND G. BIGLINO 771 SIEST 692 Identification of DP- 1904 and its Ester Glucuronide in Identification of the Urinary Metabolites of Tacrine in the Rat. ROBERT S. HSU, GREGORY M. SHUTSKE,

Human Urine and Determination ofTheir Enan- dmd.aspetjournals.org EVA M. DILEO, SUSAN M. CHESSON, ANASTASIA R. tiomeric Compositions by High Performance Liq- uid Chromatography with Optical Activity and LINVILLE, AND RICHARD C. ALLEN 779 Ultraviolet Detection. MAKOTO TANAKA, KENJI Hepatic Microsomal Metabolism of Sulfamethoxazole ON0, HIDEO HAKUSUI, TosHlo TAKEGOSHI. Y0SH- to the Hydroxylamine. ALASTAIR E. CRIBB AND IFUMI WATANABE, AND MUNEFUMI KANAO 698 STEPHEN P. SPIELBERG 784 Biotransformation of Sufentanil in Liver Microsomes Factors Affecting the Expression of Trifluoroacetylated ofRats, Dogs, and Humans. K. LAVRIJSEN, J. VAN Liver Microsomal Protein Neoantigens in Rats at ASPET Journals on September 23, 2021 HOUDT, D. VAN DYCK, J. HENDRICKX, W. LAU- Treated with Halothane. J. GERALD KENNA, WERS, R. HURKMANS, M. BOCKX, C. JANSSEN, W. JACKIE L. MARTIN, HIROK0 SATOH, AND LANCE MEULDERMANS, AND J. HEYKANTS 704 R. POHL 788

Identification of the Rabbit and Human Cytochromes The Metabolic Fate of Stiripentol in the Rat: Studies P-45OIIIA as the Major Enzymes Involved in the on Cytochrome P-450-mediated Methylenedioxy N-Demethylation of Diltiazem. LYDIANE PICHARD, Ring Cleavage and Side-chain Isomerism. KANYIN GERARD GILLET, ISABELLE FABRE, ISABELLE ZHANG, FRANCIS LEPAGE, GERARD CUVIER, DALET-BELUCHE, CLA U DE BONFILS, JEAN-PAUL JACQUES ASTOIN, MOHAMED S. RASHED, AND THENOT, AND PATRICK MAUREL 711 THOMAS A. BAILLIE 794

Metabolism of Benzene in Rat Hepatocytes: Influence The Metabolic Pathways of Tianeptine, a New Anti- of Inducers on Phenol Glucuronidation. D. depressant, in Healthy Volunteers. LUC GRISLAIN, SCHRENK AND K. W. BOCK 720 PATRICK GELE, MARC BERTRAND, WIM LUIJTEN, Distribution and Disposition ofTrospectomycin Sulfate NORBERT BROMET, CATHERINE SALVADORI, AND in the In Vito Rat, Perfused Rat Liver, and Cul- ANNIE KAMOUN 804 tured Rat Hepatocytes. JEFFREY W. Cox, L. GRA- HAM DRING, LEONARD C. GINSBERG, PHILIP G. LARSON, DEBORAH A. CONSTABLE, AND ROGER G. SHORT COMMUNICATIONS ULRICH 726 Pharmacokinetics and Protein Binding of Salicylate Influence of a Single Dose of Ethanol on the Kinetics Metabolites in Rats. MARILYN E. MORRIS 809 of Valproic Acid in Rats. I. G. ALONSO, J. M. Age-associated Alterations in Diazepam-metabolizing LANAO, M. I. MARTIN, A. MATEOS, A. D0MIN- Enzyme Activities in Male and Female Rats. SH0- GUEZ-GIL HURLE, AND J. FERMOSO 732 ICHI FUJITA, JUN TATSUNO, KENICHI KITANI, The Identification of Urinary Metabolites of Doxepin AND TOKUJI SUZUKI 812 in Patients. YUE-ZHONG SHU, JOHN W. HUBBARD, Disposition and Metabolism of Oligodeoxynucleoside JOHN K. COOPER, GORDON MCKAY, ELARIEN D. Methylphosphonate Following a Single iv Injection KORCHINSKI, RAKESH KUMAR, AND KAMAL K. in Mice. TIAN-LING CHEN, PAUL S. MILLER, PAUL MIDHA 735 0. P. Ts’o, AND 0. MICHAEL COLVIN 815 Induction of Cytochrome P-450 Isozyme 3a (P- Influence of Isoniazid, Phenobarbital, Phenytoin, Preg- 450I1E 1) in Rabbit Olfactory Mucosa by Ethanol nenolone 16ct-Carbonitrile, and f3-Naphthoflavone and Acetone. XINXIN DING AND MINOR J. COON. 742 on Halothane Metabolism and Hepatotoxicity. Excretion and Metabolism of Recainam, a New Anti- MARK A. JENNER, JOHN L. PLUMMER, AND MI- arrhythmic Drug, in Laboratory Animals and Hu- CHAEL J. COUSINS 819 Drug Metabolism and Disposition: the biological fate of chemicals

November/December 1990 Vol. 18, No. 6 CONTENTS Best Paper Award for 1989 823 Metabolism of the Anticonvulsant Agent Zonisamide in the Rat. DWIGHT D. STIFF AND MICHAEL A. The 1988 Bernard B. Brodie Award Lecture: Functional ZEMAITIS 888 Diversity of Hepatic Cytochromes P-450. WAYNE LEVIN 824 Taxol Metabolism: Isolation and Identification of Three Major Metabolites of Taxol in Rat Bile. BERNARD Pharmacokinetics and Tissue Distribution ofthe Renin MONSARRAT, ERIC MARIEL, SUZIE CROS, MICHELE Downloaded from Inhibitor N-(2-CR)-Benzyl-3-tert-butyl-sulfonyl- GARES, DANIEL GUENARD, FRANcOISE GUERITTE- propionylhischacvalNbutylamine in Marmo- VOEGELEIN, AND MICHEL WRIGHT 895 sets. F. CUMIN, C. SCHNELL, P. RICHERT, F. RASCH- DORF, A. PROBST, K. SCHMID, J. M. WOOD, AND Physiological Pharmacokinetics of a New Muscle-Re- M. DE GASPARO 831 laxant, Inaperisone, Combined with its Pharma- cological Effect on Blood Flow Rate. OSAMU NA- Dose-Dependent Pharmacokinetics of MK-4 17, a Po-

GATA, MITSUO MURATA, HIDEO KATO, TETSUYA dmd.aspetjournals.org tent Carbonic Anhydrase Inhibitor, in Rabbits Fol- TERASAKI, HIT05HI SATO, AND AKIRA TSUJI 902 lowing Single and Multiple Doses. JIUNN H. LIN, 1-WU CHEN, EDGAR H. ULM, JOHN R. GEHRET, Metabolism ofHexafluoropropene: Evidence for Bioac- AND DANIEL E. DUGGAN 836 tivation by Glutathione Conjugate Formation in the Kidney. MICHAEL KOOB AND WOLFGANG Disposition and Metabolism ofCarbovir in Mice Dosed DEKANT 911 Intravenously or Orally. S. M. EL DAREER, K. F. TILLERY, L. M. ROSE, R. F. STRUCK, AND D. L. In Vivo Metabolites of S-(2-Benzothiazolyl)-L-Cysteine

HILL 842 as Markers of In VIv() Cysteine Conjugate f3-Lyase at ASPET Journals on September 23, 2021 and Thiol Glucuronosyl Transferase Activities. Disposition of Amiodarone and its Proximate Metab- ADNAN A. ELFARRA AND IN YOUNG HWANG ... 917 olite, Desethylamiodarone, in the Dog for Oral Administration of Single-Dose and Short-Term Metabolism and Disposition of the Dopamine Agonist Drug Regimens. JAMES F. BRIEN, SANDRA JIMMO, 2-(N-Propyl-N-2-Thienylethylamino)-5-Hydroxy- F. JAMES BRENNAN, PAUL W. ARMSTRONG, AND tetralin in Conscious Monkeys after Subsequent HOSHIAR ABDOLLAH 846 Intravenous, Oral, and Ocular Administration. T. K. GERDING, B. F. H. DRENTLI, R. A. DE ZEEUW. Pharmacokinetics, N-Glucuronidation, and N4-Acety- P. G. TEPPER, AND A. S. HORN 923 lation of Sulfa-6-Monomethoxine in Humans. TOM B. VREE, ELEONORA W. J. BENEKEN KOLMER, Metabolism and Covalent Binding of [‘4CjToluene by YECHIEL A. HEKSTER, MINORU SHIMODA, MAKOTO Human and Rat Liver Microsomal Fractions and ONO. AND IADAYOSHI MIURA 852 Liver Slices. DENNIS E. CHAPMAN, TRACY J. MOORE, SANDRA R. MICIIENER, ANI)GARTII Progesterone Metabolism in Hepatic Microsomes: Ef- P0WIS 929 fect of the Cytochrome P-450 Inhibitor, Ketocon- azole, and the NADPH 5a-Reductase Inhibitor, 4- Diflunisal Disposition: Role of Gastric Absorption in MA, upon the Metabolic Profile in Human, Mon- the Development of Mucosal Damage and Anti- key, Dog, and Rat. DAVID C. SWINNEY 859 Inflammatory Potency in Rodents. BERND NUERN- BERG, ISTVAN SZELENYI, H. THOMAS SCHNEIDER, Metabolism of Citral, an a, $-Unsaturated Aldehyde, AND KAY BRUNE 937 in Male F344 Rats. J. J. DILIBERTO, P. SRINIVAS, D. OVERSTREET, G. USHA, L. T. BURKA, AND L. S. Cytochrome P-450 Isozymes Involved in Metabolic BIRNBAUM 866 Activation of s9-Tetrahydrocannabinol by Rat Liver Microsomes. SHIZUO NARIMATSU, KAZUHITO Metabolism of Diphenyl Sulfoxide in Perfused Guinea WATANABE, TAMIHIDE MATSUNAGA, IKU0 YAMA- Pig Liver: Involvement of Aldehyde Oxidase as a MOTO, SUSUMU IMAOKA, YOSHIHIKO FUNAE, AND Sulfoxide Reductase. SHIN’ICHI YOSHIHARA AND HIDETOSHI YOSHIMURA 943 KIYOSHI TATSUMI 876 The Metabolism of Etintidine in Rat, Dog, and Human. Life Span Profiles of Glutathione and Acetaminophen F. A. WONG, J. R. LLOYD, AND D. W. GRADEN.. 949 Detoxification. THERESA S. CHEN, JOHN P. RICHIE, JR., AND CALVIN A. LANG 882 Ciprofloxacin Does Not Impair the Elimination of Di- 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. Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics. (‘ontents (cont ‘d.)

azepam in Humans. W. J. A. WIJNANDS, J. F. G. EDWARD W. SZCZEPAN, LEAH C. KNICKLE, AND TROOSTER, P. C. TEUNISSEN, H. A. CATS, AND T. JOHN R. BEND 1031 B. VREE 954 Formation and Reversibility ofS-Linked Conjugates of Identification of N-Acetyl-S-(2,5-dihydroxyphenyl)-L- N-(1-Methyl-3,3-diphenylpropyl)isocyanate, an In Cysteine as a Urinary Metabolite of Benzene, Vitro Metabolite of N-(l-Methyl-3,3-diphenylpro- Phenol, and Hydroquinone. DONALD E. NERLAND pyl)formamide, in Rats. ABDUL E. MUTLIB, RASMY AND WILLIAM M. PIERCE, JR 958 E. TALAAT, J. GREG SLATTER, AND FRANK S. ABBOTT 1038 Effects of Sodium Salicylate on Elimination Kinetics of Indomethacin and Bile Production in Dogs. W. S. In Vitro Metabolism of(-)-Cis-3-[2-Hydroxy-4-(1, 1-di- BECK, K. DIETZEL, G. GEISSLINGER, H. ENGLER, methylheptyl)phenyl]-trans-4-(3-hydroxypropyl) H. VERGIN, AND K. BRUNE 962 Cyclohexanol, a Synthetic Bicyclic Cannabinoid Analog. BRIAN F. THOMAS AND BILLY R. MARTIN 1046 Disposition in Humans of Racemic Picenadol, an Opioid Analgesic. PAULA M. FRANZ, SALLY L. Species Comparison of Pharmacokinetics and Metal,- ANLIKER, JOHN T. CALLAGHAN, KARL A. DE- olism ofDiltiazem in Humans, Dogs, Rabbits, and SANTE, PATRICIA H. DHAHIR, ROBERT L. NELSON, Rats. POLLEN K. F. YEUNG, SUSAN J. MOSHER, AND ALAN RUBIN 968 MICHAEL A. QUILLIAM, AND TERRENCE J.

MONTAGUE 1055 Downloaded from Isotope Effect Studies on the Mechanism of the Cyto-

chrome P-450I1A 1-Catalyzed Formation of Pharmacokinetics of Flobufen and its Main Active Me- Testosterone from Testosterone. KENNETH R. tabolite in the Rat. ROMAN LAPKA, STANISLAV KORZEKWA, WILLIAM F. TRAGER, KIY0sHI SMOLIK, AND VACLAV REJHOLE 1060 NAGATA, ANDREW PARKINSON, AND JAMES R. GILLETTE 974 In Vitro Metabolism of Cannabichromene in Seven Common Laboratory Animals. N. K. BROWN AND dmd.aspetjournals.org Metabolic Disposition of Trimetrexate, a Nonclassical D. J. HARVEY 1065 Dihydrofolate Reductase Inhibitor, in Rat and Systemic Pharmacokinetics of Acetylenic Retinoids in Dog. BRADLEY K. WONG, THOMAS F. WOOLF, Rats. S. S. LIU, R. SANDRI, AND D. D. S. TANG- TSUN CHANG, AND LLOYD R. WHITFIELD 980 LIU 1071 Pharmacokinetics ofPropafenone Enantiomers in Rats. The Pharmacokinetics of (-)-Carbovir in Rats: Evi- REZA MEHVAR 987 dence For Nonlinear Elimination. KENNETH R.

Oxidative Defluorination of 1 , 1, l,2-Tetrafluoroethane BROUWER, ROBERT L. ST. CLAIRE, JEANNE LA- at ASPET Journals on September 23, 2021 by Rat Liver Microsomes. MICHAEL J. OisoN, GARDE, JIM PATANELLA, JOHN WALSH, AND GER- CHARLES A. REIDY, JOHN T. JOHNSON, AND ALD T. MIWA 1078 THOMAS C. PEDERSON 992 The Metabolism and Excretion of Carbovir, a Carbo- The Use of Pig Hepatocytes to Study the Biotransfor- cyclic Nucleoside, in the Rat. JOHN S. WALSH, mation offl-Nortestosterone by Pigs: Identification JAMES E. PATANELLA, STEVE E. UNGER, KENNETH of Glucuronidated 15a-Hydroxy-norandrostene- BROUWER, AND GERALD T. MIWA 1084 dione as an Important In Vitro and In Vivo Metab- olite. L. A. P. HOOGENBOOM, M. C. J. BERGHMANS, SHORT COMMUNICATIONS A. VAN VELDHUIZEN, AND H. A. KUIPER 999 Identification of a Glucuronide Conjugate of the Car- Quinolone Inhibition ofCytochrome P-450-Dependent bocyclic Nucleoside, Carbovir, Isolated from Mar- Caffeine Metabolism in Human Liver Micro- moset Urine. JAMES E. PATANELLA, JOHN S. somes. U. FUHR, T. WOLFF, S. HARDER, P. SCHY- WALSH, STEVE E. UNGER, GERALD T. MIWA, P. MANSKI, AND A. H. STAIB 1005 SIMON PARRY, MICK J. DANIEL, AND GARY L. Pulmonary Elimination and Metabolism of 5-Fluoro- EVANS 1092 2’-Deoxyuridine in Isolated Perfused Rat Lung and Identification of Phenolic Doxepin Glucuronides from Lung Slices. H. FOTH, J. HELLKAMP, E.-M. KU- Patient Urine and Rat Bile. YUE-ZHONG SHU, NELLIS,ANDG.F.KAHL 1011 JOHN W. HUBBARD, GORDON MCKAY, AND KA- Plasma Elimination and Urinary Excretion of Metha- MAL K. MIDHA 1096 pyrilene in the Rat. DANIEL W. KELLY, CLAUDE Characterization of a Quaternary, N-Glucuronide Me- L. HOLDER, WALTER A. KORFMACHER, AND WIL- tabolite of the Imidazole Antifungal, Tioconazole. LIAM SLIKKER, JR 1018 P. V. MACRAE, M. KINNS, F. S. PULLEN, AND M. Metabolism of Antiparkinson Agent Dopazinol by Rat H. TARBIT 1100 Liver Microsomes. KAMLESH P. VYAS, PRASAD H. The Metabolism of Ofloxacin in Humans. F. A. WONG KRI, HARRI G. RAMJIT, STEVEN M. PITZENBER- AND S. C. FLOR 1103 GER, AND MARTIN HICHENS 1025 The Metabolic Fate of 13-cis-Retinoic Acid in Mouse Three N-Aralkylated Derivatives of l-Aminobenzotria- Skin Microsomal Preparations. NEIL OLDFIELD.. 1105 zole as Potent and Isozyme-Selective, Mechanism- Based Inhibitors of Guinea Pig Pulmonary Cyto- Author Index 1108 chrome P-450 In Vitro. KIMBERLY J. WOODCROFT, Subject Index 1111