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Drug Metabolismand Disposition:the biological fate of chemicals

January/February 1988 Vol. 16, No. 1

CONTENTS

The 1986 Bernard B. Brodie Award Lecture. The Ge-netic Regulation of Drug-metabolizing Enzymes.DANIEL W. NEBERT

1-a-Acetylmethadol Administration to Lactating RatDams. Effect on Hepatic Aniline Hydroxylase andEthylmorphine N-Demethylase Activities in RatPups. GARY A. LESHER AND WILLIAM P.BEIERSCHMITr

In Vitro Evidence against the Oxidation of Quinidineby the Sperteine/Debrisoquine Monooxygenase ofMuman Liver. S. V. OrroN, R. U. BRINN, AND L.F. GRAM

Interspecies Comparison of Acivicin Pharmacokinetics.J. PATRICK MCGOvREN, MARTA G. WILLIAMS,AND JULIANNA C. STEWART

The Effects of Tin-Protoprophyrin Administration onHepatic Xenobiotic Metabolizing Enzymes in theJuvenile Rat. DANIEL L. STOUT AND FREDERICK F.BECKER

Polyethylene Glycol-L-asparaginase and L-AsparaginaseStudies in Rabbits. DAH HsI W. Ho, CFIIA-YINGWANG, JUAN-RU UN, NITA BROWN, ROBERT A.NEWMAN, AND IRWIN H. KRAKOFF

UDP-Glucuronosyltransferase Activity toward Digitox-

igenin-Monodigitoxoside. Differences in Activa-

tion and Induction Properties in Rat and Mouse

Liver. GEORGE A. HAZELTON AND CURTIS D.KLAASSEN

Inhibition of Rat Liver Aldehyde Dehydrogenase byAcrolein. DAVID Y. MITCHELL AND DENNIS R.PETERSEN

Effect of Monooxygenase Inducers and Inhibitors onthe Hepatic Metabolism of 2,3,7,8-Tetrachlorodi-benzo-p-dioxin in the Rat and Hamster. VICTOR J.WROBLEWSKI AND JAMES R. OI.soN

Kinetic Studies on the Competition between Famoti-dine and Cimetidine in Rats. Evidence of MultipleRenal Secretory Systems for Organic Cations.JIUNN H. LIN, LAYNE E. Los, EDGAR H. ULM, ANDDANIEL E. DUGGAN

Cyclosporine-Cimetidine Interaction. MARTIN J.D’SOUZA, STANLEY H. POLLOCK, AND HARVEY M.SOLOMON

Metabolism of 2’,3-Dichloro-l-propene in the Rat.

Consideration of Bioactivation Mechanisms. E.EDER AND K. DORNBUSCH

Metabolism of Bepridil in Laboratory Animals and

Humans. W. N. WU, J. F. HILLS, S. Y. CHANG,AND K. T. NG

‘9F NMR Spectrometry Evidence for Bile Acid Conju-gates of a-Fluoro-f3-alanine as the Main BiliaryMetabolites of Antineoplastic Fluoropynmidinesin Humans. M. C. MALET-MARTINO, J. BERNA-DOU, R. MARTINO, AND J. P. ARMAND

Biliary Excretion of a Glutathione Conjugate of Busul-fan and 1,4-Diiodobutane in the Rat. DANIEL H.

9 MARCHAND, RORY P. REMMEL, AND MAHMOUDM. ABDEL-MONEM

Neonatal Programming ofEthylmorphine Demethylaseand Corticosteroid 5a-Reductase by Testosterone,

15 Dihydrotestosterone, and Estradiol. Effects of anAnti-estrogen, an Anti-androgen, and an InhibitorofEstrogen Synthetase. EVANGELICA F. REYES AND

18 BRUCEB.VJRGOInteraction of Epicatechins Derived from Green Tea

with Rat Hepatic Cytochrome P-450. ZHI Y.WANG, MUKUL DAS, DAVID R. BICKERS, AND

23 HASAN MUKHTARIn Vivo 3P Nuclear Magnetic Resonance Studies on

the Absorption of Tnphenyl Phosphite and Tri-O-cresyl Phosphate following Subcutaneous Admin-

27 istration in Hans. CLARK D. CARRINGTON, C. TY-LER BURT, AND MOHAMED B. ABOU-DONIA

Induction of Sulfamethazine Acetylation by Hydrocor-

tisone in the Rabbit. PHILIP T. REEVES, RODNEYF. MINCHIN, AND KENNETH F. ILLm

30 . . . . . . .Regional Distnbution of Xenobiotic Metabolizing En-

zymes in the Respiratory Airways of Dogs. JAMES

A. BOND, JACK R. HARKEMA, AND V. IMOGENERUSSELL

Pharmacokinetics of Nicotine and Twelve Metabolites

in the Rat. Application of a New Radiometric High43 Performance Liquid Chromatography Assay. G. A.

KYEREMATEN, L. H. TAYLOR, J. D. DEBETHIZY,AND E. S. VESELL

Disposition of Cefixime in the Pregnant and Lactating

Rat. Transfer to the Fetus and Nursing Pup. E.

52 HALPERIN-WALEGA, V. K. BATRA, A. P. TONELLI,A. BARR, AND A. YACOBI

Potential Metabolic Basis for Enflurane Hepatitis and57 the Apparent Cross-sensitization between Enflur-

ane and Halothane. D. D. CHRIST, H. SETOH, J. G.KENNE, AND L. R. POHL

60 Pharmacokinetics and Toxicity of High Doses of Anti-body Fab Fragments in Rats. PAUL R. PENTEL,DANIEL E. KEYLER, DEBRA G. GILBERTSON,

69 GEORGE RUTH, AND SUSAN M. POND

Continued on next page

DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental Therapeutics,

428 E. Preston St., Baltimore MD 21202. Second class postage paid at Baltimore, MD and at additional mailing offices. Postmaster send address changes (Form 3579)

to the Williams & Wilkins Co., 428 E. Preston SL, Baltimore MD 21202. 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 $15.00 ($17.00 foreign). Prices subject to change. Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.

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Contents (cont ‘d.)

Metabolic Inhibition and Di-2-Ethylhexyl Phthalate SHIM0NIsHI, KAZUHITO WATANABE, IKUO YAMA-Pharmacokinetics in Fish. ADEL H. KARARA AND MOTO, AND HIDETOSHI YOSHIMURA 156WILLIAM L. HAYTON 146

Characterization of Mixed-function Oxideses and Pu- SHORT COMMUNICATIONrifled Cytochrome P-450 of Livers of House MuskShrew, Suncus murinus. K. MIZOKAMI, M. FUKU-HARA, T. NOHMI, M. SUNOUCHI, F. FUJIMORI, A. The Effect of N-Acetylcysteine on the Toxicity InducedTAKANAKA, AND Y. OM0RI 151 by N-Nitrosodimethylamine. W. A. GARLAND, E.

Enzymatic Oxidation of 7-Hydroxylated �-Tetrahy- P. NORKUS, W. A. KUENZIG, AND M. L. POWELL.drocannabinol to 7-Oxo-i�8-tetrahydrocannabinol 162by Hepatic Microsomes of the Guinea Pig. SHIZUO Books Received 166NARIMATSU, KAZUHIKO MATSUBARA, TATSUYUKI Announcement 166

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DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental Therapeutics. 428E. Preston St., Baltimore, MD 2 1202. Second class postage paid at Baltimore, MD and at additional mailing offices. POSTMASTER: Send address changes to DRUGMETABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore MD 2 1202. Price per volume: USA individual rate $60; Japan $85 (includes air freight); all othercountries $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 uponlocation, single copy $15.00 ($17.00 foreign). Prices subject to change. Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.


March/April 1988 Vol. 16, No.2

CONTENTS

Letter to the Editor: Isotope Effects on FormaldehydeOxidation. HENRY D’A. HECK AND MERCEDESCASANOVA 167

Letter to the Editor: Isotope Effects on FormaldehydeOxidation-Response. LARRY K. KEEFER, A. J.STREETER, L. Y. LEUNG, W. C. PERRY, H. S.-W.Hu, AND T. A. BAILLIE 168

Metabolic Activation of the Halothane Metabolite,[‘4C]2-Chloro-1, 1-difluoroethene, in Hepatic Mi-crosomes. MAX T. BAKER AND JAMES N.BATES 169

Regioselective and Stereoselective Metabolisms of Py-rene and l-Bromopyrene by Rat Liver Micro-

somes and Effects of Enzyme Inducers. MAGANG

SHOU AND SHEN K. YANG 173

Regiochemistry and Substrate Stereoselectivity ofO-Demethylation of Verapamil in the Presence of

the Microsomal Fraction from Rat and Human

Liver. WENDEL L. NELSON, LESLIE D. OLSEN,DANA B. BEITNER, AND ROBERT J. PALLOW,JR 184

In Vivo Renal Tubular Secretion and Metabolism ofthe Disulfide of 2,3-Dimercaptopropane-l-sulfo-nate. JAMES R. STEWART AND GARY L.DIAMOND 189

The Disposition of the Hypolipidemic Agent, O-(N-Phthalimido)acetophenone, in Sprague-DawleyRats. IRIS H. HALL, DAVID J. REYNOLDS, STEVEND. WYRICK, J. H. MAGUIRE, AND ROBERT P.SHREWSBURY

Dose-dependent Pharmacokinetics of RecombinantTissue-type Plasminogen Activator in Anesthe-tized Dogs following Intravenous Infusion.KEI-LAI L. FONG, CARL S. CRYSLER, BRUCE A.MIC0, KATHLEEN E. BOYLE, GREGORY A. KOPIA,LINDA KOPACIEWICZ, AND ROBERT K. LYNN

Regioisomenc Aromatic Dihydroxylation of Pro-pranolol. Use of Monohydroxylated Intermediatesfor Structural Assignments of the Metabolites For-med in Vitro. RASMY E. TALAAT AND WENDEL L.NELSON

Regioisomeric Aromatic Dihydroxylation of Pro-pranolol. Synthesis and Identification of 4,6- and4,8-Dihydroxypropranolol as Metabolites in theRat and in Man. RASMY E. TALAAT AND WENDELL. NELSON

Regioisomeric Products of Propranolol Metabolism.The Monomethyl Ethers of 3,4-Dihydrox-ypropranolol and of 3,4-DihydroxypropranololGlycol. LINDA M. GUSTAVSON AND WENDEL L.NELSON

Relationship between the Pharmacokinetic and Phar-

macodynamic Profile of Nilvadipine in the Dog.WEN-HUI Wu, B. MARSHALL HENDERSON, Ro-BERT LANC, DIANNE GARNES, AVRAHAM YACOBI,

AND B. MICHAEL SILBER

Dose-dependent Tissue Uptake of Flecainide duringChronic Administration in Rabbits. R. KANNANAND A. MATIN-ASGARI 228

In Vitro Metabolism and Covalent Binding among or-tho-Substituted Bromobenzenes of Varying Hepa-totoxicity. PAUL E. WELLER, N. NARASIMHAN,JOHN A. BUBEN, AND ROBERT P. HANZLIK 232

Effect of Diet and Gavage on the Absorption and Me-tabolism of Fluperlapine in the Rat. JEREMY G.DAIN AND JAMES M. JAFFE 238

Disposition and Metabolism of Double-labeled [3Hand ‘4C]N-Methyl-2-pyrrolidinone in the Rat.

DAVID A. WELLS AND GEORGE A. DIGENIS 243

Quantitative Analysis of l-Methyl-4-Phenyl-l,2,3,6-tetrahydropyridine Metabolism in Isolated RatHepatocytes. DONATO DI MONTE, T0sHIHIR0SHINKA, MARTHA S. SANDY, NEAL CASTAGNOLIJR., AND MARTYN T. SMITH

Cyclosponne-Phenytoin Interaction. MARTIN J.D’SOUZA, STANLEY H. POLLOCK, AND HARVEYM. SOLOMON 256

N-Benzylimidazole, a High Magnitude Inducer of RatHepatic Cytochrome P-450 Exhibiting Both Poly-cyclic Aromatic Hydrocarbon- and Phenobarbital-type Induction of Phase I and Phase II Metaboliz-ing Enzymes. DAMON I. PAPAC AND MICHAEL R.FRANKLIN

Cytochrome P.450-dependent Formation of Ethylene

from N-Nitrosoethylamines. XINXIN DING AND

MINOR J. COON 265

Pharmacokinetics and Tissue Distribution of Recombi-

nant Human Tumor Necrosis Factor-a in Mice.

BOBBE L. FERRAIOLO, JEROME A. MOORE, DI-ETRICH CRASE, PETER GRIBLING, HELGA WILK-

ING, AND ROBERT A. BAUGHMAN


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310 Announcement 335

Modulation of trans-4-Acetylaminostilbene Metabol-ism in the Rat by Methylcholanthrene and Phe-nobarbital and Its Relevance for Acute Toxicity.ANDREA PFEIFER AND HANS-G#{220}NTERNEUMANN

Marked Interspecies Differences between Humans andPigs in Cyclosporine and Prednisolone Disposi-tion. B. M. FREY, M. SIEBER, D. METFLER, H.GANGER AND F. J. FREY 285

Effect of Serum from Renal Failure and Cirrhotic Pa-tients on the Blood-Brain Barrier Permeability toDL-Propranolol in Rats. TSU-HAN LIN, YUICHISUGIYAMA, YASUFUMI SAWADA, SEll KAWASAKI,

TATSUJI IGA, AND MANABU HANANO

Metabolism of Cyclosporin A. III. Interaction of theMacrolide Antibiotic, Erythromycin, Using Rab-bit Hepatocytes and Microsomal Fractions. ISA-BELLE FABRE, GERARD FABRE, PATRICK

MAUREL, PIERRE BERTAULT-PERES, AND JEAN-

PAUL CAN0

The Metabolism and Disposition of Fenofibrate in Rat,Guinea Pig, and Dog. ANDRE WElL, JOHN CALD-WELL, AND MARGHERITA STROLIN-BENEDETTI.. 302

Pre- and Postweaning Development of Drug-metabo-lizing Enzyme Activities in Small Intestine andLiver of Rats. ISABELLE DE WAZIERS, MICHELB0IssET, AND SEBASTIEN ATTEBA

The Rat Biliary and Urinary Metabolism of the N6-Methylated Derivative of Elliptinium Acetate, anAntitumor Agent. Y. BRAHAM, G. MEUNIER, ANDB. MEUNIER 316

SHORT COMMUNICATIONS

Effect of pH on Acyl Migration and Hydrolysis ofTolmetin Glucuronide. MARTHA L. HYNECK,CALDIN MUNAFO, AND LESLIE Z. BENET 322

Identification of Two Metabolites of a Penem (Sch34343) in Human Urine. H. KiM, B. PRAMANIK,A. LAPIGUERA, T. M. CHAN, V. M. GIRl-JAVALLABHAN, S. SYMCHOWICZ, AND C. LIN.... 325

Efflux of Cimetidine from the Rat Cerebrospinal fluid.

HIR0SHI SUZUKI, YASUFUMI SAWADA, YUICH!

SUGIYAMA, TATSUJI IGA, AND MANABU

HANANO 328

Inhibition of Cimetidine Transport By Creatinine in

Luminal Membrane Vesicles Prepared from Rab-

bit Kidney. LEE G. GISCLON AND KATHLEEN M.GIACOMINI 331

Metabolism of 7-Ethoxyresorufin by Phenobarbital or

Aroclor 1254 Pretreated Mice. STEVEN J. GLASSAND ROBERT B. L. VAN LIER 333

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DRUG METABOLISM AND DI5POSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental Therapeutics, 428E. Preston St., Baltimore, MD 21202. Second class postage paid at Baltimore, MD and at additional mailing offices. POSTMASTER: Send address changes to DRUGMETABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore MD 21202. Price per volume: USA individual rate $60; Japan $85 (includes air freight); all othercountries $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 uponlocation, single copy $15.00 ($17.00 foreign). Prices subject to change. Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.


May/June 1988 Vol.16, No.3

CONTENTS

Enzymatic Hydrolysis of Retinamides. Tzii-WEN SHIH,Y. FULMER SHEALY, AND DONALD L. HILL 337

Genetic Control of Acetyl Coenzyme A-Dependent Ar-ylamine N-Acetyltransferase, Hydrazine N-Acetyl-transferase, and N-Hyd.roxyarylamine O-Acetyl-transferase Enzymes in C57BL/6J, A/J, AC57F1,and the Rapid and Slow Acetylator A.B6 andB6.A Congenic Imbred Mouse. DAVID W. HEIN,ALMA TRINIDAD, TOKUNBO YEROKUN, RONALD

J. FERGUSON, WARD G. KIRLIN, AND WENDELLW. WEBER

Suppression of Acetaminophen Conjugation and of

Conjugate Elimination in the Rat By Metyrapone,a Classical P.450 Inhibitor. RAYMOND E. GAL-INSKY AND GEORGE B. CORCORAN 348

Inhibition of the Metabolism of Urethane by Ethanol.T0sHIN0RI YAMAMOTO, WILLIAM M. PIERCE,JR., HARRELL E. HURST, DI CHEN, AND WILLIAMJ. WADDELL 355

Benzazepine Metabolism Revisited: Evidence for theFormation ofNovel Amine Conjugates. KENNETHSTRAUB, MARGARET DAVIS, AND BRUCE HWANG 359

Pharmacokinetics of a Series of 6-Chloro-2,3,4,5-tetra-hydro-3-substituted-lH-3-benzazepines in Rats:Determination of Quantitative Structure-Phar-macokinetic Relationships. CHARLES T. GOMBAR,ROBERT M. DEMARINIS, MARGARET WISE, ANDBRUCE A. MICO

Pharmacokinetic Procedures for the Estimation of Or-gan Clearances for the Formation of Short-LivedMetabolites: Acetaminophen-Induced Glutathi-one Depletion in Hamster Liver. RUTH CHENAND JAMES R. GILLETTE

Hydroxy Metabolites of Phencyclidine: Identificationand Quantitation of Two Novel Metabolites. DI-LIP J. GOLE, JEAN-LUC PIRAT, JEAN-MARC KA-MENKA, AND EDWARD F. DOMINO 386

Differential Renal Handling of Angiotensin-Convert-ing Enzyme Inhibitors Enalaprilat and Lisinopnlin Rats. JIUNN H. LIN, 1-WU CHEN, EDGAR H.ULM, AND DANIEL E. DUGGAN 392

Metabolism-Dependent Covalent Binding of (S)-[5-3H-]-Nicotine to Liver and Lung Microsomal

Macromolecules. M�x K. SHIGENAGA, AN-THONY J. TREVOR, AND NEAL CASTAGNOLI, JR. . 397

Excretion and Biotransformation of Cisapnde in Dogsand Humans After Oral Administration. WILLEMMEULDERMANS, ACHIEL VAN PEER, JAN

HENDRICKX, WILLIAM LAUWERS, ERIC SWYSEN,

MARC BOCKX, ROBERT WOESTENBORGHS, AND

JOSEPH HEYKANTS

Excretion and Biotransformation of Cisapride in Ratsafter Oral Administration. WILLEM MEULDER-MANS, JAN HENDRICKX, WILLIAM LAUWERS, Ro-BERT HURKMANS, ERIK MOSTMANS, ERIC

SWYSEN, JOHAN BRACKE, ALFONS KNAEPS, AND

JOSEPH HEYKANTS

Stereoselectivity and Regioselectivity of Purified Hu-man Glutathione Transferases �, a-t, and � withAlkene and Polycyclic Arene Oxide Substrates.LoRI A. DOSTAL, CLAES GUTHENBERG, BENGTMANNERVIK, AND JOHN R. BEND

Species Differences in the Stereoselective Hydrolysis ofEsmolol by Blood Esterases. CHECK Y. QUON,KHOUNG MAI, GHANSHYAM PATIL, AND HER-

MAN F. STAMPFLI 425

Metabolism and Disposition of n-Butyl Acrylate inMale Fischer Rats. J. M. SANDERS, L. T. BURKA,AND H. B. MATTHEWS 429

Methyl Carbamate: Species-Dependent Variations inMetabolism and Clearance in Rats and Mice. Y.M. IOANNOU, J. M. SANDERS, AND H. B. MAT-THEWS 435

Mechanism of Azoreduction of Dimethylaminoazeo-benzene by Rat Liver NADPH-Cytochrome P.450Reductase and Partially Purified CytochromeP-450: Oxygen and Carbon Monoxide Sensitivityand Stimulation by FAD and FMN. WALTER G.LEVINE AND HAIDER RAZA

Metabolism of l-Chloro-2-methyl-propene: Evidencefor Reactive Chloroaldehyde Intermediates. PULL-ABHATLA SRINIVAS AND LEO T. BURKA 449

Determination and Metabolism of Dithiol ChelatingAgents: III. Formation of Oxidized Metabolites of2,3-Dimercaptopropane-l-sulfonic Acid in Rab-bit. RICHARD M. MAIORINO, GREGORY L. WE-BER, AND H. VASKEN APOSHIAN

Disposition of Ethanol and its Proximate Metabolite,Acetaldehyde, in the Near-Term Pregnant Ewe forShort Term Maternal Administration of Mode-rate-Dose Ethanol. DAVID W. CLARKE, GRAEME


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N. SMITH, JOHN PATRICK, BRYAN RICHARDSON,AND JAMES F. BRIEN 464

Pharmacokinetics of Cannabidiol in Dogs. EMILSAMARA, MEIR BIALER, AND RAPHAEL

MECHOULAM 469

Distribution of [3HlColchicine in Brain and SpinalCord Areas following Its Intracerebroventricularor Intraspinal Cord Injection in Rats. PAOLAZANOLI, AUGUSTA BENELLI, MAURIZIO SAND-

RINI, AND MARIO BARALDI 473

Biotransformation of Organic Nitrate Esters In Vitroby Human Liver, Kidney, Intestine, and Blood Se-rum. FRANcIsco A. POSADAS DEL Rio, FER-NANDO JARAMILLO JUAREZ, AND ROGELIO CAM-

ACHO GARCiA

Protein-Mediated Hepatic Uptake of Rose Bengal inAnalbuminemic Mutant Rats (NAR): Albumin IsNot Indispensable to the Protein-Mediated Trans-port of Rose Bengal. SU CHIN TsAo, YUICHI SUo-IYAMA, K0N0MI SHINMURA, YASUFUMI SAW-

ANDA, SUMI NAGASE, TATSUJI IGA, AND MANABU

HANANO

Glucuronides of Hydroxylated Metabolites of Amitrip-

tyline and Nortriptyline Isolated from Rat Bile.BRUNHILDE BAIER-WEBER, A. PRox, H. WACH-SMUTH, AND URSULA BREYER-PFAFF


Influence of Platelet-Activating Factor Antagonist onCirculating Levels of Cyclosponne in the Dog. F.L. S. TSE AND H. T. SMITH 497

Quantitative Metabolic Profile of Tripelennamine andPyrilamine in the Rat. S. Y. YEH AND FU-LIANHSU 499

The Effect of Pindolol on the Transport of L-Lysinein Renal Brush Border Membrane Vesicles.POE-HIRR HSYU, FEE MI WONG, AND KATHLEEN

M. GIACOMINI 503

Identification of a Quarternary Ammonium-LinkedGlucuronide of Chlorpromazine in the Urine of aSchizophrenic Patient Treated With Chiorpro-mazine. A. K. CHAUDHARY, J. W. HUBBARD, G.MCKAY, AND K. K. MIDHA

Enantioselective Formation and Disposition of (E)-and (Z)-l0-Hydroxynortriptyline. E. NUSSER, K.NILL, AND U. BREYER-PFAFF

Intervention of Nitrite in the Metabolism of Quartern-ary Ammomum Compounds. E. N. MADUAGWU

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DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental Therapeutics, 428E. Preston St., Baltimore, MD 21202. Second class postage paid at Baltimore, MD and at additional mailing offices. POSTMASTER: Send address changes to DRUGMETABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 2 1202. Price per volume: USA inidividual rate $60; Japan $85 (includes air freight); all othercountries $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 uponlocation, single copy $15 ($17 foreign). Prices subject to change. Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.


July/August 1988 Vol. 16, No. 4

CONTENTS

Distribution of [3H]Diisopropylfluorophosphate,[3H]Soman, [3H]Sarin, and Their Metabolites inMouse Brain. P. J. LITTLE, J. A. SCIMECA, AND B.R. MARTIN 515

The Influence of Diffusional Barriers on PresystemicGut Elimination. PETER R. GWILT, SUSANNACOMER, PRAVIN R. CFIATURVEDI, AND DONALDH. WATERS 521

Effect of Galactosamine-Induced Hepatic UDP-Glu-curonic Acid Depletion on Acetaminophen Elim-ination in Rats: Dispositional Differences betweenHepatically and Extrahepatically Formed Glu-curonides of Acetaminophen and Other Chem-

icals. ZOLTAN GREGUS, CHERUKURY MADHU,DANIEL GOON, AND CURTIS D. KLAASSEN

The Disposition of [3H]Diisopropylflurophosphate inGuinea Pigs after Inhalation. JOSEPH A. SCIMECAAND BILLY R. MARTIN 534

Enatioselective Disposition and Protein Binding of[(5,6-Dichloro-9A-propyl-3-oxo-2,3,9,9a-tetra-

hydro-l-H-fluoren-7-yl)-oxy] Acetic Acid, a NewCerebral Antiedemic Agent in Rats. JIUNN H. LINAND JOHN Y.-K. HSIEH

Dose-Response Behavior of the Induction of a1-AcidGlycoprotein by Phenobarbital in the Dog. FRED

P. ABRAMSON 546

Ascorbic Acid Deficiency and Hepatic UDP-Glu-curonyltransferase. CATHERINE M. NEUMANNAND VINCENT G. ZANNONI

Distribution of Microsomal Monooxygenases in the

Rabbit Respiratory Tract. PATRICK J. SABOURIN,RONALD E. TYNES, RICHARD M. PHILPOT,SHARON WINQUIST, AND ALAN R. DAHL 557

Species-DEPENDENT BINDING OF DISOPYRAMIDE EN-

ANTIOMERS. JOHN J. LIMA 563

Disposition and Metabolism of Prinomide in Labora-tory Animals. H. EGGER, W. ITTERLY, V. JOHN,R. RODEBAUGH, C. SHIMANSKAS, F. STANCATO,AND A. KAPOOR 568

Coordinated Maternal Imprinting and Paternal Ge-notype Determined the Ultimate Level of HepaticCytochrome P.450 and Associated Monoox-ygenase Activities. VICKI J. SIMpsoN, HAIYEN E.ZHAU, MEREDITH N. RUNNER, AND LELAND W.K. CHUNG

Foreign Compound Metabolism Studies with HumanLiver Obtained as Surgical Waste: Relation to Do-nor Characteristics and Effects of Tissue Storage.G. Powis, I. JARDINE, R. VAN DYKE, R.WEINSHILBOUM, D. MOORE, T. WILKE, W.RHODES, R. NELSON, L. BENSON, AND C.SZUMLANSKI 582

Cellular and Subcellular Localization ofa Binding Pro-tein for Polychlorinated Biphenyls in Rat Lung.

JOHAN LUND, THEODORA DEVEREUX, HANS

GLAUMANN, AND JAN-AKE GUSTAFSSON 590

Metabolism of N,N-Diethyl-m-Toluamide (DEET) byLiver Microsomes from Male and Female Rats:

Simultaneous Quantitation of DEET and Its Me-tabolites by High Performance Liquid Chroma-tagraphy. JUPITA M. YEUNG AND WESLEY G.TAYLOR

Metabolism of Diazepam In Vitro by Human Liver:Independent Variability of N-Demethylation andC3-Hydroxylation. T. INABA, A. TAIT, M. NA-KANO, W. A. MAHON, AND W. KALOw 605

Biopharmaceutical Characterization of 450191-5, a

551 Ring-Opened Derivative of 1,4-Benzodiazepine.

II. Evidence for Reduced First-Pass Extraction byRat Liver. M. K0IKE, S. FUTAGUCHI, S. TAK-AHASHI, AND K. SUGENO

Stereoselective N-Oxygenation of Zimeldine and Ho-mozimeldine by the Flavin-Containing Monoox-ygenase. JOHN R. CASHMAN, JOHN PROUDFOOT,DAVID W. PATE, AND THOMAS HOGBERG 616

Stereoselective Pharmacokinetics of Ketoprofen in theRat: Influence of Route of Administration. R. T.FOSTER AND F. JAMALI 623


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Substrate Specificity and Enantioselectivity of Arylcar- Nonlinear Tissue Distribution of Ouabain in Rabbits.boxylic Acid Glucuronidation. S. FOUR- HIDEYOSHI HARASHIMA, YUICHI SUGIYAMA,NEL-GIGLEUX, C. HAMAR-HANSEN, N. M0TA5- TATSUJI IGA, AND MANABU HANANO 645SIM, B. ANTOINE, 0. MOTHE, D. DECOLIN, J.CALDWELL, AND G. SrnsT 627 SHORT COMMUNICATIONS

New Aspects of Metabolic Conjugation of Chlor- Glucuronidation in 4-Chlorbiphenyl Metabolism by

amphenicol. JEAN-MICHEL WAL, JEAN-CLAUDE Rat and Human Liver Microsomes. R. F. VOLP 650PELERAN, ELIZABETH PERDU, DINESH R,�o, AND

GEORGES BORIES 635 Effect of Enoxacin and 4-Oxo-Enoxacin on AntipyrineDisposition in the Rat. DAVID J. EDWARDS,

Possible Hemodynamic Basis to Urethane Anesthesia- NANCY M. WAITE, AND CRAIG K. SVENSSON 653Induced Reductions in Renal Clearance. M. GUM-BLETON, P. U. NICHOLLS, AND G. TAYLOR 640 Erratum 656

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DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental Therapeutics, 428E. Preston St., Baltimore, MD 21202. Second class postage paid at Baltimore, MD and at additional mailing offices. POSTMASTER: Send address changes to DRUGMETABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 2 1202. Price per volume: USA inidividual rate $60: Japan $85 (includes air freight): all othercountries $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 uponlocation, single copy $15 ($17 foreign). Prices subject to change. Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.


September/October 1988 Vol. 16, No. 5

CONTENTS

Induction of Monooxygenase Activity in the Intestine

of Spot ( Leiostomus xanthurus) a Marine Teleost,by Dietary Polycyclic Aromatic Hydrocarbons.PETER A. VAN VELD, JOHN J. STEGEMAN, BRUCER. WOODIN, JOHN S. PATTON, AND RICHARD F.LEE

Metabolism of Ethane and Pentane to Carbon Dioxide

by the Rat. M. S. DAUGHERTY, T. M. LUDDEN,AND R. F. BURK 666

Comparison of Human and Mouse Liver MicrosomalMetabolism of Bromobenzene and Chlorobenzene

to 2- and 4-Halophenols. BRENT D. KERGER,STEPHEN M. ROBERTS, AND ROBERT C. JAMES . . 672

Metabolism of Lovastatin by Rat and Human Liver

Microsomes In Vitro. MICHAEL D. GREENSPAN,JOEL B. YUDKOVITZ, ALFRED W. ALBERTS, LOISS. ARGENBRIGHT, BYRON H. ARISON, AND JACKL. SMITH

The Disposition and Toxicology of Retinyl Methyl

Ether in Rats Dosed Orally. D. MUNSELLMCPHILLIPS, CHARLES LINDAMOOD III, JAMES E.HEATH, AND DONALD L. HILL 683

Disposition and Metabolism of Sodium 4-[(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propyl)sulfonyl]-’y-

oxobenzenebutanoate in Rats and Dogs. D. J.TOCCO, F. A. DELUNA, A. E. W. DUNCAN, H. G.RAMJIT, S. M. PITZENBERGER, AND J. Y. HSIEH 690

The Physiological Disposition of Aerosolized 4-[(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propyl)sulfon-ylj-’y-oxobenzenebutanoate (L-648,05 1) in Rats.D. J. TOCCO, A. E. W. DUNCAN, F. A. DELUNA,AND G. WELLS

Enzymatic Conjugation of Hexachloro-l ,3-butadiene

with Glutathione: Formation of l-(Glutathion-S-yl)-l,2,3,4,4-pentachlorobuta-l,3-diene and 1,4-

bis(glutathion-S-yl)-l,2,3,4-tetrachlorobuta-l,3-di-

ene. WOLFGANG DEKANT, SPYRIDON VAMVAKAS,DIETRICH HENSCHLER, AND M. W. ANDERS

Metabolism of the Prodrug Dega (N-(2,6-Dime-thylphenyl)-4-[[(diethylamino)acetyljaminojbenz-

amide) to the Potent Anticonvulsant LY2OI I 16 inMice: Effect of bis-(p-Nitrophenyl)phosphate. C.JOHN PARLI, ERIC EVENSON, BRIAN D. POTTS, EDBEEDLE, RON LAWSON, DAVID W. ROBERTSON,AND J. DAVID LEANDER

Sulfation of Acetaminophen in Isolated Rat Hepato-

cytes: Relationship to Sulfate Ion Concentrationsand Intracellular Levels of 3’-Phospho-adenosine-5 ‘-Phosphosulfate. DAVID J . SWEENYAND LESTER A. REINKE

Ecdysone Catabolism in the White Mouse.

JEAN-PIERRE GIRAULT, RENE LAFONT, AND UL-

RICH KERB 716

Disposition of Citral in Male Fischer Rats. J. J. DI-LIBERTO, G. USHA, AND L. S. BIRNBAUM 721

Comparative Metabolic Disposition of Ivermectin inFat Tissues of Cattle, Sheep, and Rats.SHUET-HING LEE CHIU, JOSEPHINE R. CARLIN,RAE TAUB, ELENA SESTOKAS, JONATHAN ZWEIG,WILLIAM J. A. VANDENHEUVEL, AND THEODOREA. JACOB

Metabolism of Kadsurenone and 9, lO-Dihydrokad-surenone in Rhesus Monkeys and Rat Liver Mi-crosomes. KATHRYN L. THOMPSON, MICHAEL N.CHANG, JOHN C. CHABALA, SHUET-HING L.CHIU, DIANA ELINE, HOWARD B. HUCKER, BER-NADETTE M. SWEENEY, SAMUEL D. WHITE,BRYON H. ARISON, AND JACK L. SMITH

Phenylbutazone-Hydroxycoumarol Interactions: Ef-fects on Steady State Disposition, Hepatocellular

Distribution, and Biliary Excretion of (S)-Acenocoumarol in Rats. H. H. W. THIJSSEN, L. G.M. BAARS, AND G. M. J. JANSSEN

Cyclosporine Pharmacokinetics in Rats and Inter-

species Comparison in Dogs, Rabbits, Rats, andHumans. LORENZO SANGALLI, ANGELA B0R-TOLOTTI, LUISA JIRITANO, AND MAURIZIO Bo-

NATI


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Comparative Study on the Disposition of a NewOrally Active Dopamine Prodrug, N-(N-Acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine(TA-870) and Dopamine Hydrochloride in Ratsand Dogs. M. YOSHIKAWA, H. ENDO, M.OTSUKA, I. YAMAGUCHI, AND S. HARIGAYA .... 754

Bambuterol, a Carbamate Ester Prodrug of Ter-butaline, as Inhibitor of Cholinesterase in HumanBlood. ANDER5 TUNEK AND LEIF-A. Svensson .. 759

Studies on the Metabolism of i-Menthol in Rats. K.MADHAVA MADYASTHA AND V. SRIVATSAN .... 765


Urinary Metabolites of Rimantadine in Humans. F. R.RUBIO, E. K. FUKUDA, AND W. A. GARLAND ... 773

Pharmacokinetics of Cyclosporine in Streptozotocin-Induced Diabetic Rats. MARTIN J. D’SOUZA,HARVEY M. SOLOMON, LYDIA C. FOWLER, ANDSTANLEY H. POLLOCK 778

Books Received 781

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November/December 1988 Vol. 16, No. 6

CONTENTS

Effects of Pretreatment with the Retinoid N-(4-Hy-droxyphenyl)-all-trans-Retinamide and Phenobar-bital on the Disposition and Metabolism of N-(4-Hydroxyphenyl)-all-trans-Retinamide in Mice.THERESA A. HULTIN, DAVID L. MCCORMICK,CYNTHIA M. MAY, AND RICHARD C. MOON . ...

Renal Transepithelial Transport of Nucleosides. J.ARLY NELSON, ELENA VIDALE, AND MOFOLO-

RUNSOENIGBOKAN 789

Identification of Ibopamine Metabolites in Rat andDog Urine. GEORGE Y. Kuo, BRUCE Y.-H.HWANG, AND ROBERT K. LYNN 793

In Vivo Rat Hemoglobin Thiyl Free Radical Forma-tion Following Administration of Phenylhydrazineand Hydrazine-Based Drugs. KIRK R. MAPLES,SANDRA J. JORDAN, AND RONALD P. MASON . . . 799

Virginiamycin Metabolism in Cattle Rumen Fluid.DAVID W. GOTTSCHALL, RICHARD WANG, ANDDAVID G. I. KINGSTON 804

In Vivo Radical Trapping and Biliary Secretion of Rad-ical Adducts of Carbon Tetrachioride-DerivedFree Radical Metabolites. KATHRYN T. KNECHTAND RONALD P. MASON 813

O-Dephenylation and Conjugation with Benzoylor-nithine: New Metabolic Pathways for 3-Phenox-ybenzoic Acid in Chickens. GARY B. QUISTAD,ANNETTE L. SAUNDERS, WAYNE S. SKINNER,KATHERINE D. COLLIER, DAMON H. SAKAI, ANDCAROL C. REUTER

Sexual Dimorphism of Nicotine Metabolism and Dis-tribution in the Rat: Studies in Vivo and in Vitro.G. A. KYEREMATEN, G. F. OWENS, B. CHAT-TOPADHYAY, J. D. DEBETHIZY, AND E. S. VESELL 823

Renal Handling of 5-Nitrofuran Nephrotoxins in the

Rat. S. BALLAL, L. A. SPRY, T. V. ZENSER, AND B.B. DAVIS 829

Regiochemistry and Enantioselectivity in the OxidativeN-Dealkylation of Verapamil. WENDEL L.NELSON AND LESLIE D. OLSEN 834

Bioavailibility of Benzo(a)pyrene Desposited in the

Lung: Correlation with Dissolution from UrbanAir Particulates and Covalently Bound DNA Ad-ducts. SAM TORNQUIST, MARTIN NICKLASSON,

PETER SODERKVIST, LARS NYBOM, AND RUNETOFTGARD 842

Pharmacokinetics and Enterohepatic Recirculation of

2-n-Propyl-4-pentenoic Acid in the Rat. KULDEEP

SINGH, JAMES M. ORR, AND FRANK S. ABBOTT 848

Disposition and Metabolism of Letosteine in Rats. F.GACHON, C. NICOLAS, J. C. MAURIZIS, M.VERNY, J. L. CHABARD, M. FAURIE, AND G.GAILLARD 853

Stereoselective Metabolism and Pharmacokinetics of

Disopyramide Enantiomers in Humans. PASCALLE CORRE, DENIS GIBASSIER, PIERRE SADO, AND

ROGER LE VERGE 858

Structure-Tissue Distribution Relationship Based onPhysiological Pharmacokinetics for NY-l98, ANew Antimicrobial Agent, and the Related Py-ridonecarboxylic Acids. EIICHI OKEZAKI, TET-SUYA TERASAKI, MASATO NAKAMURA, OSAMU

NAGATA, HIDEO K�To, AND AKIRA TSUJI

Pharmacokinetics of the Dimethylheptyl Homolog of

Cannabidiol in Dogs. EMIL SAMARA AND MEIRBIALER 875

Mechanism for Inhibitory Effect of Cannabidiol onMicrosomal Testosterone Oxidation in Male RatLiver. SHIzU0 NARIMATSU, KAZUHITO WAT-

ANABE, IKUO YAMAMOTO, AND HIDETOSHI

YOSHIMURA


DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental Therapeutics, 428E. Preston St., Baltimore, MD 21202-3993. Second class postage paid at Baltimore, MD and at additional mailing offices. POSTMASTER: Send address changes toDRUG METABOLISM AND DISPOSITION, 428 E. Preston St., Baltimore, MD 21202-3993. Price per volume: USA individual rate $65; Japan $ 102 (includes airfreight); all other countries $80 surface mail. USA institutional rate $100 Japan $137 (includes air freight); all other countries $1 15 surface mail; air printed matters pricesavailable on request; single copy $ 15 ($ 18 foreign). Prices subject to change. Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeu-tics.

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Parallel Induction of Plasma a-Acid GlycoproteinConcentration and Antipyrine Clearance by Var-ious Doses of Phenobarbital in the Dog. FRED P.ABRAMSON 890

N-Chenodeoxycholyl-2-fluoro-�3-alanine: A Biliary Me-tabolite of 5-Fluorouracil in Humans. DAVID J.SWEENY, MICHAEL MARTIN, AND ROBERT B. DI-ASIO 892

Comparison of Cyclosporine A and G Phar-macokinetics. MARTIN J. D’SOUZA, KEROP B.GOURDIKIAN, AND ADELINA L. MUJUKIAN 895

Obesity as a Risk Factor in Drug Induced Organ In-jury. II. Increased Renal Cytochrome P-450 in theObese Overfed Rat. GEORGE B. CORCORAN ANDDANIEL E. SALAZAR 898

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