Drug Metabolism and DispositIon: the biological fate of chemicals

January/February 1989 Vol. 17, No. 1 CONTENTS

Effect of Tick-Borne Fever (Ehrilichia phagocytophila) Characterization of a Carbamic Acid Ester Glu- and Trypanosomiasis ( Trypanosoma brucei 1066) curonide of the Secondary Amine, Sertraline. on the Pharmacokinetics of Suiphadimidine and LARRY M. TREMAINE, JUSTIN G. STROH, AND its Metabolites in Goats. H. VAN GOGH, A. D. J. ROBERT A. RONFELD 58 WATSON, J. F. M. Nouws, J. NIEUWENHUIJS, Downloaded from Stereoselective Oxidation of Nilvadipine, a New Dihy- AND A. S. J. P. A. M. VAN MIERT dropyridine Calcium Antagonist, in Rat and Dog Selective Mechanism-Based Inactivation of the Major Liver. TosHiRo NIWA, YoJI TOKUMA, KIKUKO Phenobarbital-Inducible P.450 Cytochrome from NAKAGAWA, AND HIDEYO NOGUCHI 64 Rabbit Liver by Phenyclidine and its Oxidation Identification of Two Main Urinary Metabolites of Product, the Iminium Compound. YOICHI OsAWA [‘4CjOmeprazole in Humans. LARS RENBERG, AND MINOR J. COON 7 dmd.aspetjournals.org ROGER SIMONSSON, AND KURT-JURGEN Metabolism of Atrial Natriuretic Peptide: Extraction HOFFMANN 69 by Organs in the Rat. PHILIP A. KRIETER AND AN- 8(S)-(Glutathione-S-YL)Dihydromorphinone, a Novel GELO J. TRAPANI 14 Metabolite of Morphine from Guinea Pig Bile. Activities of Cytosolic and Microsomal Drug Oxidases TAKASHI ISHIDA, Y0sHITO KUMAGAI, YURIKA of Rat Hepatocytes in Primary Culture. A. J. IKEDA, KENICHI ITO, MASASHI YANO, SATOSHI SHERRATT AND L. A. DAMANI 20 TOKI, KUNIHIDE MIHASHI, TOSHIHIRO FUJIYOKA, 77 at ASPET Journals on September 30, 2021 Selective Inactivation of Rat Liver Cytochromes P-450 YUKIKO IWASE, AND SHIzUK0 HACHIYAMA . ... Central Nervous System Kinetics of Atenolol by 2 1-Chlorinated Steroids. JAMES HALPERT, Metoprolol in the Dog during Long-Term Treat- JOHN-YAN JAW, LINDA J. CORNFIELD, CELIA ment. T. ABRAHAMSSON, E. LIGNELL, A. MIK- BALFOUR, AND EUGENE A. MASH 26 ULSKI, S.-G. OLovSoN, AND C.-G. REGARDH 82 Effect of Organ Perfusion on Renal Drug Transport: The Pharmacokinetics of Salicylate in the Pregnant Application to Furosemide in the Isolated Per- Wistar Rat. MARGARET DEAN, STAN PENGLIS, fused Rat Kidney. LING-JAR LEE AND DAVID E. AND BERESFORD STOCK 87 SMITH 32 Temporal Variations in the Pharmacokinetics of Iso- Inhibition of 3-Methylindole Bioactivation by the Cy- niazid and N-Acetylisoniazid in Rats. PIERRE M. tochrome P-450 Suicide Substrates 1-Am- BELANGER, MARCEL LALANDE, FRANCOIS M. inobenzotriazole and a-Methylbenzylaminoben- DORE, AND GASTON LABRECQUE 91 zotriazole. JEANNETT C. HUIJZER, JAMES D. In Vivo and in Vitro Pharmacokinetic Differences be- ADAMS, JR., JOHN-YAN JAW, AND GAROLD S. tween Four Structurally Closely Related An- YOST 37 thracyclines in Hematopoietic Cell Subtypes in Isolation and Identification of 6-Desmethylnaproxen Humans. PAUL A. J. SPETH, PETER C. M. LIN- Sulfate as a New Metabolite of Naproxen in Hu- SSEN, EMIEL F. S. TERMOND, JAN B. M. BOEZE- man Plasma. CHIN-HEN KIANG, CAROL LEE, AND MAN, HANS M. C. WESSELS, AND CLEMENS STANLEY KUSHINSKY 43 HAANEN 98

Fluconazole Is a Potent Inhibitor of Antipyrine Metab- Pulmonary Toxicity of Trichloroethylene in Mice: Co- valent Binding and Morphological Manifestations. olism in Vivo in Mice. IGNAzI0 LA DELFA, QUAN MING ZHU, ZHENGJI Mo, AND TERRENCE F. P. G. FORKERT AND D. W. BIRCH 106 BLASCHKE 49 SHORT COMMUNICATION Cilastatin-Insulin Interaction in the Rat. GREGORY C. TOMPKINS, LANE J. BRUNNER, AND DAVID R. Hepatic Drug Metabolism in Female Fischer Rats as a LUKE Function of Age. LORA E. RIKANS 114

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 inidividual rate $60; Japan $85 (includes air freight): all other countries $70 surface mail. USA institutional rate $95: Japan $120 (includes air freight): all other countries $105 surface mail and $95 to $105 air mail depending upon location. single copy $15 ($17 foreign). Prices subject to change. Copyright (C) 1989 by the American Society for Pharmacology and Experimental Therapeutics. Drug MetabolIsm and Disposition: the biological fate of chemicals

March/April 1989 Vol. 17, No. 2 CONTENTS

Methoxyflurane Enhances Allyl Alcohol Hepatotoxic- N-Methylation as a Toxication Route for Xenobiotics. ity in Rats: Possible Involvement of Increased Ac- II. In Vivo Formation of N,N’-Dimethyl-4,4’-bi- rolein Formation. WILLIAM C. KERSHAW, DEBO- pyridyl Ion (Paraquat) from 4,4’-Bipyridyl in the RAH A. BARSOTrI, THOMAS B. LEONARD, JOHN G. Guinea Pig. C. STEVEN GODIN AND PETER A. DENT, AND GARY L. LAGE 117 CROOKS Downloaded from The Covalent Binding to Protein of Valproic Acid and Spironolactone Metabolism in Target Tissues: Charac- Its Hepatotoxic Metabolite, 2-n-Propyl-4-penten- teristics ofDeacetylation in Kidney, Liver, Adrenal oic Acid, in Rats and in Isolated Rat Hepatocytes. Cortex, and Testes. N. LYNN FLOWERS, JOHN P. O’DONNELL, AND HOWARD D. COLBY 186 DAVID J. PORUBEK, MARK P. GRILLO, AND THOMAS A. BAILLIE 123 Renal Tubular Secretion of Amioride and Its Inhibi-

tion by Cimetidine in Humans and in an Animal dmd.aspetjournals.org A Characterization of Chlordecone Pretreatment-alter- Model. ANDREW A. SOMOGYI, CHRISTOPHER M. ed Pharmacokinetics in Mice. HILLARY M. CAR- HOVENS, MURRAY R. MUIRHEAD, AND FELIX PENTER AND LAWRENCE R. CURTIS 131 BOCHNER 190

Role of Pharmacokinetics and Metabolism in the En- Metabolism of Cyclosporin A. IV. Purification and hanced Susceptibility of Middle-aged Male Spra- Identification of the Rifampicin-Inducible Human gue-Dawley Rats to Acetaminophen Nephrotoxic- Liver Cytochrome P-450 (Cyclosporin A Oxidase)

ity. JOAN B. TARLOFF, ROBIN S. GOLDSTEIN, BRUCE as a Product of P4501 1 1A Gene Subfamily. JEAN at ASPET Journals on September 30, 2021 A. MIco, AND JERRY B. HOOK 139 COMBALBERT, ISABELLE FABRE, GERARD FABRE, ISABELLE DALET, JN DERANcOURT, JEAN PAUL Effect of Experimental Diabetes on Elimination Kinet- CANO, AND PATRICK MAUREL 197 ics of Diflunisal in Rats. JIUNN H. FLORENCIA

A. DELUNA, DOMINICK J. Toxo, AND EDGAR H. The Pharmacokinetics of Albumin Conjugates of - ULM 147 Penicillamine in Rats. DAVID A. JOYCE, DENIS N. WADE, AND BARBARA R. SWANSON 208 Cocaine Disposition in Humans after Intravenous In- Stereoselective Metabolism and Pharmacokinetics of jection, Nasal Insufflation (Snorting), or Smoking. Racemic Methylphenobarbital in Humans. WENG A. ROBERT JEFFcOAT, MARIO PEREZ-REYES, Ju- HUA LIM AND WAYNE D. HOOPER 212 DITH M. HILL, BRIAN M. SADLER, AND C. EDGAR CooK 153 Metabolic Interaction between Morphine and Nalox- one in Human Liver A Common Pathway of On the Antipyrine Test in Laboratory Animals: Studies Glucuronidation? AGNETA WAHLSTROM, KERSTIN in the Dog and Monkey. F. F. VICKERS, T. A. PERSSON, AND ANDERS RANE 218 BOWMAN, B. H. DVORCHIK, 0. T. PASSANANTI, D. M. HUGHES, AND E. S. VESELL 160 SHORT COMMUNICATIONS

The Physiological Disposition of Lovastatin. D. E. Species Differences in Protein Binding of Diflunisal. DUGGAN, I.-W. CHEN W. F. BAYNE, R. A. HALPIN, JIUNN H. LIN 221 C. A. DUNCAN, M. S. SCHWARTZ, R. J. STUBBS, AND S. VICKERS 166 Tissue Distribution of Intravenously Administered Di- methyl Sulfoxide in the Normal Rat. MERRY C. Pharmacokinetics and Metabolism of SK&F 86002 in NISHIMURA, PEYTON JACOB III, MARY E. CASSEL, Male and Female Sprague-Dawley Rats. J. F. NEW- AND LAWRENCE H. Pirrs 224 TON, L. P. Y0DI5, D. KEOHANE, R. ECKARDT, R. DEWEY, J. DENT, AND B. MIGG 174 Erratum 227

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 $60; Japan $85 (includes air freight); all other countries $70 surface mail. USA institutional rate $95; Japan $120 (includes air freight); all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15 ($17 foreign). Prices subject to change. Copyright © 1989 by the American 5ociety for Pharmacology and Experimental Therapeutics. Drug Metabolism and Disposition: the biological fate of chemicals

May/June 1989 Vol. 17, No. 3 CONTENTS

In Memoriam 229 Quantitation of Multiple Pathways for the Metabolism of Nephrotoxic Cysteine Conjugates Using Selec- Identification and Kinetic Characterization of Acetyla- tive Inhibitors of L-a-Hydroxy Acid Oxidase (i- tor Genotype-dependent and -independent Ary- Amino Acid Oxidase) and Cysteine Conjugate lamine Carcinogen N-Acetyltransferases in Ham- ster Bladder Cytosol. TOKUNBO YEROKUN, WARD 13-Lyase. JAMES L. STEVENS. PAUL B. HATZINGER,

297 Downloaded from G. KIRLIN, ALMA TRINIDAD, RONALD J. FERGU- AND PATRICK J. HAYDEN SON, FREDRICK OGOLLA, ALLEN F. ANDREWS, Disposition ofthe Radioprotector Ethiofos in the Rhe- PAMELA K. BRADY, AND DAVID W. HEIN 231 sus Monkey: Influence ofRoute of Administration. Kinetic Characterization of Acetylator Genotype-de- DONALD J. MANGOLD, MICHAEL A. MILLER, Bi- pendent and -independent N-Acetyltransferase Iso- LINDA K. HUELLE, DAWN 0. T. SANCHEZ-BARONA, zymes in Homozygous Rapid and Slow Acetylator NOLLIE F. SWYNNERTON, LAWRENCE FLECKEN-

Inbred Hamster Liver Cytosol. ALMA TRINIDAD, STEIN, AND THOMAS 0. LUDDEN 304 dmd.aspetjournals.org WARD G. KIRLIN, FREDRICK OGOLLA, ALLEN F. Metabolism of Bambuterol in Rat Liver Microsomes: ANDREWS, TOKUNBO YEROKUN, RONALD J. FER- Identification of Hydroxylated and Demethylated GUSON, PAMELA K. BRADY, AND DAVID W. HEIN 238 Products by Liquid Chromatography Mass Spec- Nasal Absorption and Metabolism of Progesterone and trometry. CLAES LINDBERG, CLAES Roos, ANDERS l7f3-Estradiol in the Rat. RIMA N. BAWARSHI- TUNEK, AND LEIF A. SVENSSON 311 NASSAR, ANWAR A. HUSSAIN, AND PETER A. Metabolism of the Antimycotic Agent, Croconazole, CROOKS 248 in Rabbits. MASAYUKI NAKANO, YoslilKAzu at ASPET Journals on September 30, 2021 Human Intestinal Phenol Sulfotransferase: Assay Con- NAKAJIMA, K0UJI IWATANI, YUJI lKENlSIll, ditions, Activity Levels and Partial Purification of Yuzo NAKAGAWA, AND K0ICHI SUGENO 323 the Thermolabile Form. RAJAH S. SUNDARAM, CAROL SZUMLANSKI, DIANE OTFERNESS, JON A. Haloperidol Reductase in Human and Guinea Pig

VAN LOON, AND RICHARD M. WEINSHILBOUM ... 255 Livers. T. INABA AND J. KOVACS 330

Characteristics of Warfarin Hydroxylation Catalyzed Evidence in Humans for Variant Allozymes of the by Human Liver Microsomes. ALLAN E. RETTIE, Non-deficient Sparteine/Debrisoquine Mono- A. CRAIG EDDY, LARRY D. HEIMARK, MIL0 GI- oxygenase (P45OIID1) In Vitro. R. F. TYNDAI.E. BALDI, AND WILLIAM F. TRAGER 265 T. INABA, AND W. KALOW 334

Some Factors Affecting Phencyclidine Biotransforma- Transport of Acetaminophen Conjugates in Isolated tion by Human Liver and Placenta. ROMAN Rat Hepatocytes. SATOFUMI IIDA, TAKASHI Ml- POHORECKI, WILLIAM RAYBURN, WILLIAM W. ZUMA, N0RIK0 SAKUMA, MASAHIRO HAYASHI, AND COON, AND EDWARD F. DOMINO 271 SHOJI AWAZU 341

dentification of Etretinate Metabolites in Human Bile. FLOIE M. VANE, CHRISTOPHER J. L. BUGGE, AND SHORT COMMUNICATIONS LOLITA C. RODRIGUEZ 275

Identification of Etretinate Metabolites in Human Synthesis and Hydrolytic Behavior of the Sulfate Con- jugate of 2 ‘-Hydroxy-3,4,4’-trichlorocarbanilide. Blood. FLOIE M. VANE, CHRISTOPHER J. L. BuGGE, JOHN CRAIG, LARRY GRUENKE, HELEN N0RTII- AND LOLITA C. RODRIGUEZ 280 ROOT, AND NEAL CORBIN 345 Stereochemical Inversion of Haloxyfop in the Fischer 344 Rat. M. J. BARTELS AND F. A. SMITH 286 Stimulation of in Vitro Bioactivation of Hydroquinone by Phenol in Bone Marrow Cells. VANGALA V. Isolation of 10 Cyclosporine Metabolites from Human SUBRAHMANYAM, ALBERT SADLER, ERIC SUBA, Bile. C. PAUL WANG, NEIL R. HARTMAN, RAMAN AND DAVID Ross 348 VENKATARAMANAN, IAN JARDINE, FU-TYAN LIN, JOSEPH E. KNAPP, THOMAS E. STARZI, AND GIL- Carbonyl Sulfide: A Copper Chelating Metabolite of BERT J. BURCKART 292 Disulfiram. BENNY JOHANSSON 351

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 2 1202-3993. Price per volume: USA individual rate $60: Japan $85 (includes air freight): all other countries $70 surface mail. USA institutional rate $95: Japan $120 (includes air freight): all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15 ($17 foreign). Prices subject to change. Copyright c 989 h’ the American Society for Pharmacology and Experimental Therapeutics. Drug Metabolism and Disposition: the biological fate of chemicals

July/August 1989 Vol. 17, No. 4 CONTENTS

Investigations of the N-Hydroxylation of 3’-Hydroxy- Plasma Pharmacokinetics and Urinary Excretion of acetanilide, a Non-hepatotoxic Positional Isomer Thalidomide After Oral Dosing in Healthy Male of Acetaminophen. MOHAMED S. RASHED, AN- Volunteers. TIAN-LING CHEN, GEORGIA B. VOGEL-

THONY J. STREETER, AND SIDNEY D. NELSON .... 355 SANG, BRENT G. PErrY, ROBERT B. BRUNDRETr, DENNIS A. N0E, GEORGE W. SANTOS, AND 0. Isozyme-specific Monoclonal Antibody-directed As- MICHAEL COLVIN 402 sessment of Induction of Hepatic Cytochrome P- Hydroxylation of 4.4’-Methylenebis(2-chloroaniline) Downloaded from 450 by Clotrimazole. WASIUDDIN A. KHAN, CHRIS- by Canine, Guinea Pig, and Rat Liver Microsomes. TINE KUHN, HANS F. MERK, SANG S. PARK, HARRY T. H. CHEN, B. I. KU5LIKI5, AND W. E. BRASELTON, V. GELBOIN, DAVID R. BICKERS, AND HASAN JR . 406 MUKHTAR 360 Direct Determination of Diastereomeric Carprofen Influence of Nutritional Status on the Pharmacoki- Glucuronides in Human Plasma and Urine and

netics and Pharmacodynamics of Pentobarbital. Preliminary Measurements of Stereoselective Met- dmd.aspetjournals.org DONALD JUNG AND PRATAPA P. PRASAD 365 abolic and Renal Elimination After Oral Admin- istration of Carprofen in Man. SEIGO IWAKAWA, TOSHIYUKI SUGANUMA, SHII-FUENG LEE. HILDE- Pharmacokinetics ofRecombinant Human Tumor Ne- crosis Factor-alpha in Rats: Effects of Size and GARD SPAHN, LESLIE Z. BENET, AND EMIL T. LIN 414 Number of Doses and Nephrectomy. B. L. FER- Disposition ofFlavodilol in Laboratory Animals. MARY RAIOLO, HOLLENBACH, J. MCCABE, S. B. HULT- COAN AND Ro SIMMONS 420 GREN, R. Prrrl, AND H. WILKING 369

Dose-dependent Kinetics of Cilastatin in Laboratory at ASPET Journals on September 30, 2021 Pharmacokinetics and Excretion of the 2 1-Aminoster- Animals. JIUNN H. LIN, 1-Wu CHEN, AND EDGAR oid Antioxidant U-74006F in Rat and Perfused H. ULM 426 Rat Liver. JEFFREY W. Cox, PHILIP G. LARSON, Glucuronidation of E-10-Hydroxynortriptyline in Hu- MICHAEL A. WYNALDA, VIRENDRA K. SOOD, MI- man Liver, Kidney, and Intestine: Organ-specific CHAEL T. VERBURG, AND ROBERT H. PULLEN ... 373 Differences in Enantioselectivity. MARJA-LIISA DAHL-PUUSTINEN, ETIENNE DUMONT, AND LEIF The Role of Flavin-containing Monooxygenase in the BERTILSSON 433 N-Oxidation of the Pyrrolizidine Alkaloid Sene- cionine. DAVID E. WILLIAMS, RALPH L. REED, Doxofylline in Rat Brain in Relation to Locomotor BOGDAN KEDZIERSKI, DANIEL M. ZIEGLER, AND Activity. CARLO CRAVANZOLA, MARIA CAMILLA DONALD R. BUHLER 380 REBOANI, GI0RGI0 GROSA, AND JosE SEBASTIAN FRANZONE 437 Bioactivation and Detoxication of the Pyrrolizidine 3,3’,4,4’-Tetrachlorobiphenyl: Excretion and Tissue Alkaloid Senecionine by Cytochrome P-450 En- Retention of Hydroxylated Metabolites in the zymes in Rat Liver. DAVID E. WILLIAMS, RALPH Mouse. E. KLASSON WEHLER. A. BERGMAN, I. L. REED, BOGDAN KEDZIERSKI, GHAZI A. DAN- BRANDT, P. 0. DARNERUD. AND C. A. WACHT- NAN, F. PETER GUENGERICH, AND DONALD R. MEISTER 441 BUHLER 387 In Vitro Formation of an Inhibitory Complex Between In Vitro Metabolic Degradation of a Bovine Growth an Isosafrole Metabolite and Rat Hepatic Cyto- Hormone-Releasing Factor Analog LEU27- chrome P-450 PB-B. MICHAEL MURRAY AND GOR- bGRF(l-29)NH2 in Bovine and Porcine Plasma: DON F. REIDY 449 Correlation with Plasma Dipeptidylpeptidase Ac- tivity. TERESA KUBIAK, COLLEEN KELLY, AND Studies of Metabolic Pathways of Trimebutine by Si- LAVERN KRABIL 393 multaneous Administration of Trimebutine and Its Deuterium-labeled Metabolite. YUJI MIURA, An Active, Aldehydic Metabolite of the Cell-differen- SUSUMU CHISIMA, AND SHIGEYUKI TAKEYAMA... 455 tiating Agent Hexamethylene Bisacetamide. BABU Oxidation of Tenoxicam by Leukocyte Peroxidases and SABRAMANYAM, PATRICK S. CALLERY, MERRILL J. HO2 Produces Novel Products. S. ICHIHARA, H. EGORIN, STUART SNYDER, AND BARBARA A. TOMI5AWA, H. FUKAZAWA, M. TATEISHI, R. JOLY, CONLEY 398 ANDR.HEINTZ 463

DRUG METABOLISM AND DISPOSITION (I5SN 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 $60: Japan $85 (includes air freight): all other countries $70 surface mail. USA institutional rate $95: Japan $ 120 (includes air freight): all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15 ($17 foreign). Prices subject to change. Copyright c 1989 by the American Society for Pharmacology and Experimental Therapeutics. Drug Metabolism and Disposition: the biological fate of chemicals

September/October 1989 Vol. 17, No. 5 CONTENTS

Inhibition of the Localization and Metabolism of Ure- Human and Dog, But Not Rat, Isolated Hepatocytes thane in the Mouse by Dimethyl Sulfoxide Have Decreased Foreign Compound-metabolizing (DMSO). WILLIAM J. WADDELL, CAROLYN MAR- Ability Compared to Liver Slices. G. P0wIS, D. C. LOWE, TOSHINORI YAMAMOTO, AND MARY Jo MELDER, AND T. J. WILKE 526 CLARK 469 Biotransformation of Tipredane, A Novel Topical Ste- roid, in Mouse, Rat, and Human Liver Homoge- The Pharmacokinetics ofEtretinate and Its Metabolites

nates. S. J. LAN, L. M. SCANLAN, S. H. WEINSTEIN, Downloaded from in the Dog. PHENSRI THONGNOPNUA, JOSEPH W. R. K. YARMA, B. M. WARRACK, S. E. UNGER, M. MASSARELLA, AND CHERYL L. ZIMMERMAN 473 A. PORUBCAN, AND B. H. MIGDALOF 532 Metabolism of Acrylonitrile to 2-Cyanoethylene Oxide Metabolism and Disposition of the 4-HT Uptake in F-344 Rat Liver Microsomes, Lung Micro- Blocker Sertraline in the Rat and Dog. LARRY M. somes, and Lung Cells. ALAN E. ROBERTS, STEVEN TREMAINE, WILLARD M. WELCH, AND ROBERT A. A. LACY, DENI5 PILON, MAX J. TURNER, JR., AND RONFELD 542 dmd.aspetjournals.org DOUGLAS E. RICKERT 481 Cytochromes P-450 in Murine Lung: An Immunohis- Characteristics of Monooxygenase-mediated Covalent tochemical Study with Monoclonal Antibodies. P. Binding of Methoxychior in Human and Rat Liver G. FORKERT, M. L. VESSEY, S. S. PARK, H. V. Microsomes. WILLIAM H. BULGER AND DAVID GELBOIN, AND S. P. C. COLE 551 KUPFER 487 First-Pass Metabolism of Salicylamide: Studies in the Once-Through Vascularly Perfused Rat Intestine- Pharmacokinetics and Metabolism of a 4’-Methylthio

Liver Preparation. XIN XU, HIR0KI HIRAYAMA, at ASPET Journals on September 30, 2021 Derivative of Propranolol in the Dog. S. A. BAI, AND K. SANDY PANG 556 D. E. EA5TERLING, M. J. WILSON, U. K. WALLE, C. A. HANEY, N. P. Pm, J. K. PRUETT, AND T. Deimidazolation of Antimycotic Croconazole Through WALLE 495 Epoxide Formation in Rabbit Liver Microsomes. MASAYUKI NAKANO AND KENJI MIz0JIRI 564 Age-related Changes in the Disposition of Benzyl Ace- tate: A Model Compound for Glycine Conjugation. In Vitro Studies of Human Liver Alcohol Dehydroge- nase Variants Using a Variety of Substrates. JEAN- TIMOTHY F. MCMAHON, JANET J. DILIBERTO, AND INE P. KAssAM, BING K. TANG, DEzso KADAR, LINDA S. BIRNBAUM 506 AND WERNER KALOW 567

Metabolic Conversion of 2-Propylpentanal Acetals to Systemic Intestinal Metabolism of 1-Naphthol: A Study Vaiproic Acid In Vitro: Model of Prodrugs of Car- in the Isolated Vascularly Perfused Rat Small In- boxylic Acid Agents. DOMENICK VICCHIO AND PA- testine. MICHIEL H. DE VRIES, GERARD A. H0F- TRICK S. CALLERY 513 MAN, ANDRIES 5j. KO5TER, AND JAN NOORDHOEK 573 Disposition, Metabolism, and Excretion of U-7l038, A The Influence of Phenobarbital Administration on He- Novel Renin Inhibitor Peptide, in the Rat. JOHN patic Monooxygenase Activity at Various Stages of C. GREENFIELD, KATHLEEN J. COOK, AND IRVING Gestation in the Rat. MARGARET E. DEAN AND A. O’LEARY 518 BERESFORD H. STOCK 579

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 $60; Japan $85 (includes air freight); all other countries $70 surface mail. USA institutional rate $95; Japan $120 (includes air freight); all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15 ($17 foreign). Prices subject to change. Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics. Drug Metabolism and Disposition: the biological fate of chemicals

November/December 1989 Vol. 17, No. 6 CONTENTS

Best Paper of 1988 Metabolism, Disposition, and Pharmacokinetics of a Potent Anticonvulsant, 4-Amino-N-(2,6-Dime- Disposition and Pharmacokinetics of Naltrexone After thylphenyl)benzamide (LY2O1 1 16), in Rats. Intravenous and Oral Administration in Rhesus BRIAN D. Porrs, STEVE GABRIEL, AND C. JOHN Monkeys. RICHARD H. REUNING, SUSAN B. AsH- PARLI 656 CROFT, JAMES N. WILEY, AND BRENT E. MORRISON 583 In Vivo Metabolism of Isoxicam in Rats, Dogs, and

Comparative Pharmacokinetics of 3’-Azido-3’-deoxy- Monkeys. THOMAS F. WOOLF, ANN BLACK, JAMES Downloaded from thymidine (AZT) and 3’-Azido-2’,3 ‘-dideoxyuri- L. HICKS, HELEN LEE, CHE C. HUANG, AND TSUN dine (AZddU) in Mice. KOKILA J. DOSHI, JAMES CHANG 662 M. GALLO, F. DOUGLAS BOUDINOT, AND CHUNG Physiological Disposition of CGS 16617 in Rat, Dog, K. CHU 590 and Man. H. EGGER, G. KOCHAK, P. ROBERTSON,

Pharmacokinetic Analysis ofCyclosporine in Adjuvant R. IANNUCCI, F. A. RUFINO, AND F. STANCATO .. 669 Arthritic Rats. STANLEY H. POLLOCK, HEWITT W. Oral Idazoxan Bioavailability in Rat: Relevance of In-

MATTHEWS, AND MARTIN J. D’SOUZA 595 testinal and Hepatic First-Pass Effect. J. VALLES, J. dmd.aspetjournals.org Enterohepatic Circulation of T-2 Toxin Metabolites in PRU?ZJONOSA, A. MENARGUES, M. NOMEN, AND R. the Rat. KATHLEEN A. CODDINGTON, STEVEN P. OBACH 673 SWANSON, ASLAM S. HASSAN, AND WILLIAM B. Dose-related Effects of Phenobarbital on Hepatic Glu- BUCK 600 tathione S-transferase Activity and Ligandin Levels Metabolism of a Nitrogen-containing Steroid by Rat in the Rat. HIROKAI OKUDA, BARRY J. POTTER, Hepatocytes and Hepatic Subcellular Fractions. BRIGETrE BLADES, TERESA A. MCHUGH, NATALIE GREGORY L. KEDDERIS, LOIS S. ARGENBRIGHT, L. JACOBS, AND PAUL D. BERK 677

JOHN S. WALSH, JACK L. SMITH, RALPH A. Biotransformation of 5-(2-Chloroethyl)-2’-deoxyuri- at ASPET Journals on September 30, 2021 STEARNS, BYRON A. ARISON, AND GERALD T. dine in Male NMRI Mice. I. SZINAI AND E. DE MIWA 606 CLERCQ 683 Metabolism, Disposition, and Mutagenicity of 2,6- The Uptake of Clodronate (Dichloromethylene Bis- Diaminotoluene, a Mutagenic Noncarcinogen. phosphonate) by Macrophages In Vivo and In Vi- MICHAEL L. CUNNINGHAM, LEO T. BURKA, AND tro. JUKKA MONKKONEN, ARTO URTTI, PETFERI H. B. MATTHEWS 612 PARNONEN, HEIKKI A. ELO, AND PAULI YLITALO. 690 Biotransformation of Etretinate and Developmental Sensitivity of the Rat Liver Microsomal Oxidation of Toxicity of Etretin and Other Aromatic Retinoids Pyrazole to Antibody Raised Against the Ethanol- in Teratogenesis Bioassays. D. M. KOCHHAR, J. D. inducible Rabbit Liver Cytochrome P-450 Iso- PENNER, AND L. M. MINUTELLA 618 zyme. LIvIU A. CLEJAN, DENNIS R. Koo, AND Metabolism of the Antianxiety Drug Buspirone in the ARTHUR I. CEDERBAUM 694 Rat. HEMANT K. JAJOO, ROBERT F. MAYOL, JOHN Disposition of Sandostatin, a New Synthetic Somato- A. LABUDDE, AND IAN A. BLAIR 625 statin Analogue, in Rats. M. LEMAIRE, M. AZRIA, Metabolism of the Antianxiety Drug Buspirone in Hu- R. DANNECKER, P. MARBACH, A. SCHWEITZER, man Subjects. HEMANT K. JAJOO, ROBERT F. AND G. MAURER 699 MAY01, JOHN A. LABUDDE, AND IAN A. BLAIR.. 634 Amiodarone-Digoxin Interaction in Rats: A Reduction The Pharmacokinetics of (3H)l-(l-(2-Thienyl)cyclo- in Hepatic Intake. CHANTAL LAMBERT, DANIEL hexyl)piperidine (TCP) in Sprague-Dawley Rats. LAMONTAGNE, HELEN HOTTLET, AND PATRICK DU MARK ZORBAS, S. MICHAEL OWENS, LAURA M. SOUICH 704 PLUNKETT, AND HOANG BUI 641 Influence of Pregnancy on the Pharmacokinetic Dis- position of Two Aromatic Retinoids (Etretinate SHORT COMMUNICATION and Acitretin) in the Rat. I. Intravenous Studies. KENNETH R. BROUWER AND PATRICK J. Regional Differences in Adrenal Activation of Spiron- olactone: Relationship to Steroid 17a-Hydroxylase MCNAMARA 646 Influence of Pregnancy on the Pharmacokinetic Dis- Activity. J. H. SHERRY, P. B. JOHNSON, M. LEVITT, position of Two Aromatic Retinoids (Etretinate J. BERGSTROM, AND H. D. COLBY 709 and Acitretin) in the Rat. II. Single and Multiple Author Index 711 Oral Dosing Studies. KENNETH R. BROUWER AND PATRICK J. MCNAMARA 652 Subject Index 713

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 1 202-3993. Second class postage paid at Baltimore, MD and at additional mailing offices. POSTMASTER: Send address changes to DRUG MEt ABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 2 1 202-3993. 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 $15.00 ($18.00 foreign). Prices subject to change. Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics.