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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 St., Baltimore MD 21202. Price per volume: USA individual rate $60; all other countries $70 surface mail. USAinstitutional rate $95; all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15.00 ($17.00 foreign). Prices subject tochange. Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.

Drug Metabolismand Disposition:the biological fate of chemicals

January/February 1987 Vol. 15, No. 1

CONTENTS

Bromoboenzene Metabolism in the Rat and GuineaPig. K. LERTRATANANGKOON AND M. G. HORN-

ING

Mechanisms of Lidocaine Kinetics in the Isolated Per-fused Rat Liver. I. Effects of Continuous Infusion.Y. K. TAM, M. YAU, R. BERZINS, P. R. MONTGOM-

ERY,ANDM.GRAY 12

Mechanisms of Lidocaine Kinetics in the Isolated Per-fused Rat Liver. II. Kinetics of Steady State Elim-ination. BRADLEY A. SAVILLE, MURRAY R. GRAY,ANDYUNK.TAM 17

Mechanisms of Lidocaine Kinetics in the Isolated Per-fused Rat Liver. III. Evaluation of Liver Modelsfor Time-Dependent Behavior. MURRAY R. GRAY,BRADLEY A. SAVILLE, AND YUN K. TAM 22

The Series-Compartment Model for Hepatic Elimina-tion. MURRAY R. GRAY AND Y. K. TAM

Microsomal Metabolism of Pyrrolizidine Alkaloids

from Senecio jacobaea: Isolation and Quantifica-

lion of 6,7-Dihydro-7-Hydroxy- 1-Hydroxymethyl-5H-Pyrrolizine and N-Oxides by High Perform-

ance Liquid Chromatography. HOWARD S. RAMS-DELL, BOGDAN KEDZIERSKI, AND DONALD R.BUHLER

The Formation of Procainamide Hydroxylamine byRat and Human Liver Microsomes. ROBERT A.BUDINSKY, STEPHEN M. ROBERTS, EUGENE A.COATS, LOUIS ADAMS, AND EVELYN V. Hi�ss .... 37

Studies on the Pharmacokinetics and Metabolism of 4-

Chiorodiphenyl Ether in Rats. Y. C. CHuI, R. F.ADDISON, AND F. C. P. LAW 44

Effect of Diffusional Barriers on Drug and Metabolite

Kinetics. INES A. M. DE LANNOY AND K. SANDYPANG 51

Cytochrome P-450 Isozymes 2 and 5 in Rabbit Lungand Liver: Comparisons of Structure and Induci-bility. ZAHRA PARANDOOSH, VALERIE S. FUJITA,MINOR J. COON, AND RICHARD M. PHILPOT .... 59

Extrahepatic Expression of N-Acetylator Genotype inthe Inbred Hamster. DAVID W. HEIN, WARD G.

KIRLIN, FREDERICK OGOLLA, AND ALMA TRINI-

DAD 68

Metabolism of the �-Carbolines, Harmine and Harmol,

by Liver Microsomes from Phenobarbitone- or 3-Methylcholanthrene-Treated Mice: Identificationand Quantitation of Two Novel Harmine Metab-olites. D. J. TWEEDIE AND M. D. BURKE

Stereochemical Aspects of the Glutahtione S-Transfer-

ase-Catalyzed Conjugations of Alkyl Halides.RICHARD E. RIDGEWELL AND MAHMOUD M. AB-

DEL-MONEM 82

Comparative Metabolism and Disposition of l-Chloro-

and 3-Chloro-2-methylpropene in Rats and Mice.

BURHAN I. GHANAYEM AND LEO T. BURKA 91

Microbial Transformation of the Antihistamine Pyril-amine Maleate: Formation of Potential Mamma-lian Metabolites. EUGENE B. HANSEN, JR., CARL

E. CERNIGLIA, WALTER A. KORFMACHER, DWIGHT

W. MILLER, AND ROBERT H. HEFLICH

Disposition and Biotransformation of Quinpirole, aNew D-2 Dopamine Agonist AntihypertensiveAgent, in Mice, Rats, Dogs, and Monkeys. N. G.GALLICK WHITAKER AND T. D. LINDSTROM 107

27 Characterization of the Induction of Cytosolic and Mi-crosomal Epoxide Hydrolases by 2-EthylhexanoicAcid in Mouse Liver. Bo LUNDGREN, JOHAN MEl-

JER, AND JOSEPH W. DEPIERRE 114

Deacetylation of Diltiazem by Rat Liver. ELIZABETH

LEBOEUF AND ODETFE GRECH-BELANGER 122

32 Plasma Concentration-Response Relationship for Ci-metidine Inhibition of Drug Metabolism in theRat. ADEDAYO ADEDOYIN, LEON AARONS, AND J.BRIAN HOUSTON 127

SHORT COMMUNICATIONS

Comparison of Adenosine 3’-Phosphate 5 ‘-Phospho-sulfate Concentrations in Tissues from Different

Laboratory Animals. ELZBIETA A. BRZEZNICKA,

GEORGE A. HAZELTON, AND CURTIS D. KLAASSEN 133

Influence of Age on Intrinsic Clearance of Bupivacaine

and Its Reduction by Cimetidine in Elderly MaleRats. GARY A. THOMPSON, JANE A. MYERS, PA-

TRICIA A. TURNER, DENNIS E. COYLE, WOLFGANG

A. RITSCHEL, AND DONALD D. DENSON

Effect of Surgery on Serum a-Acid Glycoprotein Con-centration and Serum Protein Binding of DL-Pro-pranolol in Phenobarbital-Treated and Untreated

Rats. TSU-HAN LIN, YUICHI SUGIYAMA, YASUFUMI

SAWADA, YASUYUKI SUZUKI, TATSUJI IGA, AND

MANABU HANANO

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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 2 1202. 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 St., Baltimore MD 21202. Price per volume: USA individual rate $60; all other countries $70 surface mail. USAinstitutional rate $95; all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15.00 ($17.00 foreign). Prices subject tochange. Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.

262


March/April 1987 Vol. 15, No.2

CONTENTS

Relationship between Sulfotransferase Activity and Sus-ceptibility to Acetaminophen-induced Liver Ne-crosis in the Hamster. MARION G. MILLER AND

DAVID J. JOLLOW 143

Dose-dependent Pharmacokinetics of Ibuprofen in theRat. A. SHAH AND D. JUNG 151

Nonenzymatic Bioreduction in Rat Liver and Kidneyof Nitroxyl Spin Labels. Potential Contrast Agentsin Magnetic Resonance Imaging. ULF G. ERIKS-

SON, ROBERT C. BRASCH, AND THOMAS N. TOZER 155

In Vitro Microsomal Metabolism of the Leukotnene

Receptor Antagonist, 5-(2-Dodecylphenyl)-4, 6-di-thianonanedioic Acid (SK&F 102,08 1). JOHN F.NEWTON, KENNETH M. STRAUB, RICHARD H.DEWEY, CARL D. PERCHONOCK, THOMAS B. LEoN-ARD, MARY E. MCCARTHY, JOHN G. GLEASON,

AND REGINA D. ECKARDT

In Vivo Metabolism of the Leukotnene Receptor An-

tagonist, 5-(2-Dodecylphenyl)-4,6-dithianonane-dioic Acid (SK&F 102,08 1) in the Guinea Pig.JOHN F. NEWTON, KENNETH M. STRAUB, GEORGEY. KUO, CARL D. PERCHONOCK, MARY E. MC-

CARTHY, JOHN G. GLEASON, AND ROBERT K.LYNN

Alterations in Biliary Excretory Function by Strepto-zotocin-induced Diabetes. JOHN B. WATKINS III

AND THOMAS P. DYKSTRA 177

Uptake, Metabolism, and Secretion of 3’-Methyl-N,N-dimethyl-4-aminoazobenzene by Isolated PerfusedRat Liver. AUDREY R. SAMUELS, LORENZ THEIL-MANN, YACOV R. STOLLMAN, ALLAN W. W0L-KOFF, AND MADHU M. BHARGAVA

Uptake and Disposition of Putrescine, Spermidine, and

Spermine by Rabbit Lungs. SHRINIVAS B. RAO AND

HARIHARA M. MEHENDALE 189

Conversion of Melphalan to 4-(Glutathionyl)phen-ylalanine. A Novel Mechanism for Conjugation by

Glutathione-S-transferases. DEANNE M. DULIK

AND CATHERINE FENSELAU 195

Conversion of N,N-Dimethylaniline to N,N-Dimeth-ylaniline-N-oxide by a Cytosolic Flavin-containingEnzyme from Trypanosoma cruzi. MOISES AGOSIN

AND GERALD T. ANKLEY 200

Pharmacokinetic Interaction between Theophylline

and Chloramphenicol in Rats. M. BUSBY AND L.J. LESKO 204

The Pharmacokinetics of All-trans-retinoic Acid andN-(2-Hydroxyethyl)retinamide in Mice as Deter-mined with a Sensitive and Convenient Procedure.Solid-phase Extraction and Reverse-phase High

Performance Liquid Chromatography. D. MUN-

SELL MCPHILLIPS, JACK R. KALIN, AND D. L.HILL

Urinary Excretion Kinetics of Famotidine in Rats.JIUNN H. LIN, LAYNE E. Los, EDGAR H. ULM, AND

DANIEL E. DUGGAN 212

In Vivo and in Vitro Biotransformaton of Theobromineby Phenobarbital- and 3-Methylcholanthrene-in-ducible Cytochrome P-450 Monooxygenases inRat Liver. Role of Thiol Compounds. CAROL A.SHIVELY AND ELLIOT S. VESELL

Effects of Aging on the Properties of Rhesus MonkeyLiver Microsomal NADPH-Cytochrome c (P-450)Reductase. DOUGLAS L. SCHMUCKER AND ROSE K.WANG 225

Extraction of w- and w-1-Hydroxylaunc Acids withEthyl Acetate Results in Formation of AcetoxyProducts. A. S. SALHAB, J. APPLEWHITE, M. W.COUCH, R. T. OKITA, AND K. T. SHIVERICK 233

Biotransformation of Caffeine, Paraxanthine, Theo-phylline, and Theobromine by Polycyclic Aro-matic Hydrocarbon-inducible Cytochrome(s) P-450 in Human Liver Microsomes. MONICA E.CAMPBELL, DENIS M. GRANT, TADANOBU INABA,ANDWERNERKALOW

Pharmacokinetics of Tetrabenazine and Its Major Me-tabolite in Man and Rat. Bioavailability and DoseDependency Studies. REZA MEHVAR, FAKHREDDINJAMALI, MICHAEL W. B. WATSON, AND DAVID

SKELTON

Flavin-containing Monooxygenase Activity in HumanLiver Microsomes. M. E. MCMANUS, I. STUPANS,W. BURGESS, J. A. KOENIG, P. DE LA M. HALL,AND D. J. BIRKETT 256

Metabolism of Ethyl 2-(4-Chlorophenyl)-5-(2-furyl)-ox-azole-4-acetate, a New Hypolipidemic Agent, inthe Rat, Rabbit, and Dog. Glucuronidation of Car-boxyl Group and Cleavage of Furan Ring. TSU-TOMU KOBAYASHI, HIDEHIRO ANDO, JUKO SUGI-HARA, AND SHOICHI HARIGAYA

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Mitotane (1 -(o-Chlorophenyl)- 1-(p-chlorophenyl)-2,2-

dichioroethane) Metabolism in Perfusion Studieswith Dog Adrenal Glands. J. E. SINSHEIMER AND

CORINNE J. FREEMAN 267

Comparison of Hepatic and Renal Metabolism of Ac-

etaminophen in Male and Female MiniatureSwine. JAMES 0. PEGGINS, TIMOTHY F. MCMAHON,WILLIAM P. BEIERSCHMITr, AND MYRON WEINER 270

In Vivo Inhibition of Phenacetin Oxidation by SuicideSubstrate l-Aminobenzotnazole. BRUCE A. MIco,DEBRA ANN FEDEROWICZ, ERIC BURAK, AND

JAMES E. SWAGZDIS 274

Pharmacogenetic Association between the Formationof 4-Hydroxymephenytoin and a New Metabo-lite of S-Mephenytoin in Man. P. J. WEDLUND,

B. J. SWEETMAN, G. R. WILKINSON, AND R. A.

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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 2 1202. 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 St., Baltimore MD 21202. Price per volume: USA individual rate $60: all other countries $70 surface mail. USAinstitutional rate $95; all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15.00 ($17.00 foreign). Prices subject tochange. Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.


May/June 1987 Vol. 15, No.3

CONTENTS

Hepatic UDP-glucose and UDP-glucuronic Acid Syn-

thesis Rates in Rats during a Reduced Energy State.RUSSELL L. DILLS, STANLEY R. HOWELL, AND

CURTIS D. KLAASSEN 281

Metabolism and Distribution of ‘4C- and 35S-LabeledCarbon Disulfide in Immature Rats of DifferentAges. ELIZABETH GREEN SNYDERWINE AND AN-

DREA HUNTER 289

In Vivo and in Vitro l-Methylxanthine Metabolism inthe Rat. Direct Evidence That the Dehydrogenase

Form of Xanthine Oxida.se Predominates in IntactPerfused Liver. LESTER A. REINKE, MITSUTAKA

NAKAMURA, LANCE LOGAN, H. Dlx CHRISTENSEN,

AND JOHN M. CARNEY

Pharmacokinetic and Deuterium Isotope Effect Studieson the Metabolism of Formaldehyde and Formate

to Carbon Dioxide in Rats in Vivo. LARRY K.KEEFER, ANTHONY J. STREETER, Louis Y. LEUNG,WILLIAM C. PERRY, HENRY S.-W. Hu, AND

THOMAS A. BAILLIE

3,4-Dichlorobenzyloxyacetic Acid Is Extensively Me-tabolized to a Taurine Conjugate in Rats. RICHARD

C. PEFFER, DONALD J. ABRAHAM, MICHAEL A.ZEMAITIS, LAN K. WONG, AND JOHN D. ALVIN . . 305

Diazepam Metabolism in Cultured Hepatocytes fromRat, Rabbit, Dog, Guinea Pig, and Man. R. J.CHENERY, A. AYRTON, H. G. OLDHAM, P. STAND-

RING, S. J. NORMAN, T. SEDDON, AND R. KIRBY. 312

Disposition of 8-Methoxypsoralen in the Rat. Induction

of Metabolism in Vivo and in Vitro and Identifi-cation of Urinary Metabolites by ThermosprayMass Spectrometry. DENNIS C. MAYS, STEPHEN G.HECHT, STEVE E. UNGER, CHRISTINE M. PACULA,

JEANETrE M. CLIMIE, DALE E. SHARP, AND NICHO-

LAS GERBER

Effects of Cisplatin-induced Nephrotoxicity on Genta-micin Pharmacokinetics in Rats. MEHER S. ENGI-

NEER, GERALD P. BODEY, SR., ROBERT A. NEW-MAN, AND DAH-HSI W. Ho 329

Induction and Inhibition of Rat Hepatic Drug Metab-

olism by N-Substituted Imidazole Drugs. JOSEPH

K. RITrER AND MICHAEL R. FRANKLIN 335

Influence of Cytochrome b5 on the Stoichiometry of

the Different Oxidative Reactions Catalyzed byLiver Microsomal Cytochrome P-450. INGELAJANSSON AND JOHN B. SCHENKMAN 344

The Formation of a Glutathione Conjugate Derivedfrom Propranolol. H. A. SASAME, D. J. LIBERATO,

AND J. R. GILLETFE 349

The Oxidation of Acrolein by Rat Liver AldehydeDehydrogenases. Relation to Allyl Alcohol Hepa-totoxicity. LORA E. RIKANS 356

The Disposition and Elimination of Two SequentialDoses of 2,4,5,2’,4’,5 ‘-Hexachlorobiphenyl. L0RI

A. GALLENBERG AND MARY Jo VODICNIK 363

Absorption, Distribution, Metabolism, and Excretionof l,2-Dihydro-2,2,4-trimethylquinoline in the

Male F344 Rat. Y. M. IOANNOU, L. T. BURKA, J.M. SANDERS, M. P. MOORMAN, AND H. B.MATrHEWS

Pharmacokinetics of Griseofulvin in Blood and Skin

Suction Blister Fluid of Rats. M. SCHAFER-

KORTIN 374

Tissue Distribution, Disposition, and Metabolism of

Cyclosporine in Rats. 0. WAGNER, E. SCHREIER,

F. HEITZ, AND G. MAURER 377

Metabolism of Cyclosporin A. I. Study in Freshly Iso-lated Rabbit Hepatocytes. GERARD FABRE, PIERRE

BERTAULT-PERES, ISABELLE FABRE, PATRICK MAU-

REL, SYLVAINE JUST, AND JEAN-PAUL CANO 384

Metabolism of Cyclosporin A. II. Implication of theMacrolide Antibiotic Inducible Cytochrome P-4503c from Rabbit Liver Microsomes. PIERRE BER-

TAULT-PERES, CLAUDE BONFILS, GERARD FABRE,

SYLVAINE JUST, JEAN-PAUL CANO, AND PATRICKMAUREL

Urinary Metabolites in Busulfan in the Rat. MOUSTA-PHA HASSAN AND HANS EHRSSON 399

Liver Metabolism of Budesonide in Rat, Mouse, andMan. Comparative Aspects. S. EDSBACKER, P. AN-

DERSSON, C. LINDBERG, J. PAULSON, A. RYRFELDT,

AND A. THALEN 403

Metabolic Acetal Splitting of Budesonide. A NovelInactivation Pathway for Topical Glucocorticoid,s.S. EDSBACKER, P. ANDERSSON, C. LINDBERG, A.RYRFELDT, AND A. THALEN 412


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Glutathione Conjugation of 1,2-Dibromo-l-phenyl-ethane in Rats in Vivo. C. E. M. ZOETEMELK, W.VAN HOVE, W. L. J. VAN DER LAAN, B. VAN MEE-

TEREN-WALCHLI, A. VAN DER GEN, AND D. D.BREIMER 418

N-Hydroxymethyl Metabolites of 45019 1-S, a 1H-1,2,4-Triazolyl Benzophenone Derivative, in DogPlasma. M. KOIKE, R. NORIKURA, S. FUTAGUCHI,

T. YAMAGUCHI, K. SUGENO, K. IWATANI, Y. IKEN-

ISHI, AND Y. NAKAGAWA 426


Plasma Concentration Proffles of Human RecombinantInterleukin-2 (HrIL-2)in the Rat following Admin-istration by Various Systemic Routes. W. A. COL-

BURN, J. HAKIMI, AND I. BEKERSKY 429

Dose- and Time-dependent Effect of Levamisole on theElimination of Antipyrine in the Rat. CRAIG K.SVENSSON AND LI-LING LIu 432

Announcements 435

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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 2 1202. 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 St., Baltimore MD 21202. Price per volume: USA individual rate $60; all other countries $70 surface mail. USAinstitutional rate $95; all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15.00 (S 17.00 foreign). Prices subject tochange. Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.


July/August 1987 Vol. 15, No.4

CONTENTS

Commentary: Renal Transport Processes and Glutathi-one Conjugate-mediated Nephrotoxicity. TERR-

ENCE J. MONKS AND SERRINE S. LAU 437

Species Differences in Disposition of Benzo[a]pyrene.ERIC H. WEYAND AND DAVID R. BEVAN 442

Uptake, Toxicity, and Distribution of Benzo[a]pyreneand Monooxygenase Induction in the Topmin-nows Poeciliopsis monacha and Poeciliopsis lucida.KATHRYN A. GODDARD, R. JACK SCHULTZ, AND

JOHN J. STEGEMAN

Determination of Metabolite Pharmacokinetics forOrally Administered Prodrugs. GREGORY M. Ko-CHAK AND ASHOK RAKHIT 456

The Metabolism and Elimination of Pyrilamine Ma-

leate in the Rat. DANIEL W. KELLY AND WILLIAM

SLIKKER, JR 460

N-Debenzylation of Pyrilamine and Tripelennamine inthe Rat. A New Metabolic Pathway. S. Y. YEH . . 466

Species-dependent Glucuronidation of Drugs by Im-mobilized Rabbit, Rhesus Monkey, and Human

UDP-glucuronyltransferases. DEANNE M. DULIKAND CATHERINE FENSELAU 473

Metabolism and Disposition of Ethylene Glycol Mon-

obutyl Ether (2-Butoxyethanol) in Rats. BURHANI. GHANAYEM, LEO T. BURKA, J. M. SANDERS, AND

H. B. MATTHEWS 478

Phencyclidine Iminium Ion. NADPH-dependent Me-

tabolism, Covalent Binding to Macromolecules,and Inactivation of Cytochrome(s) P-450. M. K.P. HOAG, A. J. TREVOR, A. KALIR, AND N. CAS-

TAGNOLI, JR

Stereoselectivity of Naphthalene Epoxidation by

Mouse, Rat, and Hamster Pulmonary, Hepatic,

and Renal Microsomal Enzymes. A. R. BUCKPITF,

N. CASTAGNOLI, JR., S. D. NELSON, A. D. JONES,

AND L. S. BAHNSON

Comparative Defluorination and Cytochrome P450Loss by the Microsomal Metabolism of Fluoro-and Fluorochloroethenes. MAX T. BAKER, JAMES

N. BATES, AND SUSAN V. LEFF 499

Noncovalent Binding of 3’-Methyl-N,N-dimethyl-4-

aminoazobenzene and Its Metabolites to Liver Cy-

tosolic Proteins and Its Role in Their NuclearTranslocation. KRISHNAPURA SRINIVASAN, WAL-TER 0. LEVINE, AND MADHU M. BHARGAVA .... 504

Effect of Cytochrome P450 and Flavin-containingmonooxygenase Modifying Factors on the in VitroMetabolism of Amiodarone by Rat and Rabbit.ROBERT A. YOUNG AND HARIHARA M.MEHENDALE

An Investigation of the Antigenic Determinants onChloroperoxidase and Purified Rat Liver Micro-somal Cytochrome P-450b. RAMENDRA N.PANDEY, STEVEN C. KUEMMERLE, AND PAUL F.

HOLLENBERG

Effects of Genetic or Chemically Induced Diabetes on

Imipramine Metabolism. Respective Involvementof Flavin Monooxygenase and Cytochrome P450-dependent Monooxygenases. E. ROUER, A. LE-

MOINE, T. CRESTEIL, P. ROUET, AND J.P. LEROUX

Stereoselective Metabolism of 2-Phenylpropionic Acidin Rat. I. In Vitro Studies on the StereoselectiveIsomerization and Glucuronidation of 2-Phenyl-

propionic Acid. YUTAKA NAKAMURA AND To-SHIRO YAMAGUCHI

Stereoselective Metabolism of 2-Phenylpropionic Acidin Rat. II. Studies on the Organs Responsible forthe Optical Isomerization of 2-PhenylpropionicAcid in Rat in Vivo. TOSHIRO YAMAGUCHI AND

YUTAKA NAKAMURA

Physiologically Based Pharmacokinetics of Radioiodi-nated Human �3-Endorphin in Rats. An Applica-

tion of the Capillary Membrane-limited Model.HIT0SHI SATO, YUICHI SUGIYAMA, YASUFUMI SA-

WADA, TATSUJI IGA, AND MANABU HANANO . ...

The Metabolism of Roxatidine Acetate Hydrochloride.Liberation of Deutenum from the Piperidine Ring

during Hydroxylation. SEIJIRO HONMA, SATOSHIIWAMURA, REIKO KOBAYASHI, YosHIHIR0 K�-WABE, AND KENYU SHIBATA

6-Fluoro-2-methylspiro(chroman-4, 4’-imidazolidine)-2,5’-dione and Related Compounds as Inducers ofMonooxygenase in Rat Liver Microsomes. TOHRU

HORIE, MITSUKAZU KITADA, HIDEHUMI YosH-

IOKA, YosHlo KANAKUBO, AND TSUNEO OMURA.

Disposition of Nafimidone in Rats. D. J. M. GRAHAM,

K. M. HAMA, S. A. SMITH, L. KURZ, M. D. CHAP-

LIN, AND D. J. HALL 565

Inhibition and Induction of Hepatic Drug Metabolismin Rats and Mice by Nafimidone and Its Major

Metabolite Nafimidone Alcohol. W. R. RUSH, S.A. SMITH, J. H. MULVEY, D. J. M. GRAHAM, AND

M. D. CHAPLIN 571


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SHORT COMMUNICATIONS BURKE, KEITH R. HUCKLE, DAVID H. HuTsoN,AND PETER MILLBURN 581

A Phenolic Metabolite of Phencyclidine: The Fonna-The Metabolic Fate of Oxazepam in Mice. S. F. SISEN tion of a Pharmacologically Active Metabolite by

WINE, C. 0. Tb, A. L. LIU, AND J. F. P0� Rat Liver Microsomes. SHIGERU OwrA, HIROSHI

TOWSKI MASUMOTO, KAORU TAKEUCHI, AND MASAAKI

HIROBE 583

Formation of the Taurine Conjugate of Benzoic Acid Books Received 585in Rainbow Trout, Salmo gairdneri. ALISON B. Announcement 586

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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 2 I 202. 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 St., Baltimore MD 21202. Price per volume: USA individual rate $60; all other countries $70 surface mail. USAinstitutional rate $95: all other countries $105 surface mail and $95 to $105 air mail depending upon location, single copy $15.00 ($17.00 foreign). Prices subject tochange. Copyright (cj 1987 by the American Society for Pharmacology and Experimental Therapeutics.


September/October 1987 Vol. 15, No.5

CONTENTS

Letter to the Editor: Criteria for the Acceptability ofExperimental Evidence for the Enantiomeric Com-

position of Xenobiotics and Their Metabolites.JOHN CALDWELL AND BERNARD TESTA 587

The Metabolism ofthe Abortifacient Terpene, (R)-(+)-Pulegone, to a Proximate Toxin, Menthofuran. W.

PERRY GORDON, ALAIN C. HUITRIC, CYNTHIA L.SETH, ROBERT H. MCCLANAHAN, AND SIDNEY D.NELSON

The Disposition and Metabolism of 2’,3’-Dideoxycy-tidine, an in Vitro Inhibitor of Human T-Lympho-trophic Virus Type III Infectivity, in Mice andMonkeys. JAMES A. KELLEY, CHARLES L. LITTERST,JERI S. ROTH, DAVID T. VISTICA, DAVID G.POPLACK, DAVID A. COONEY, MOHAN NADKARNI,

FRANK M. BALlS, SAMUEL BRODER, AND DAVID G.JOHNS

Influence of a Purified Diet and Route of Administra-

tion on the Metabolism and Disposition of Estra-diol in B6C3F1 Mice. FLOYD R. FULLERTON,DAVID L. GREENMAN, AND JOHN F. YOUNG . . . . 602

Distribution of trans-4-Hydroxy-2-hexenal and Tan-

dem Mass Spectrometric Detection of Its UrinaryMercapturic Acid in the Rat. CARL K. WINTER, H.J. SEGALL, AND A. DANIEL JONES 608

The Role of the Liver in Mediating the Acute Toxicityof the Pesticide Methyl Parathion in the Mouse.LESTER G. SULTATOS 613

Ketorolac Tromethamine Absorption, Distribution,Metabolism, Excretion, and Pharmacokinetics inAnimals and Humans. EDWARD J. MROSZCZAK,FRANK W. LEE, DANIEL COMBS, FRANK H.SARNQUIST, BEE-LIAN HUANG, ANNE T. WU,LASZLO 0. TOKES, MICHAEL L. MADDOX, AND

DIANE K. CHO

Pharmacokinetics and Pharmacodynamics of Physo-stigmine in the Rat after Intravenous Administra-tion. SATU M. SOMANI AND ABDUL KHALIQUE . . . 627

Oxidation of the Alcohol Dehydrogenase Inhibitor Pyr-azole to 4-Hydroxypyrazole by Microsomes. Effect

of Cytochrome P450 Inducing Agents. DENNIS E.FEIERMAN AND ARTHUR I. CEDERBAUM 634

Disposition of the Monoclonal Antibody-Ymca Alka-

loid Conjugate, KS1/4-DAVLB (LY256787), inFischer 344 Rats and Rhesus Monkeys. MARSHALL

E. SPEARMAN, R. MICHAEL GOODWIN, AND

DONALD KAU

Mechanism-based Inhibition of Cytochrome P450 byHeterocyclic Analogues of Phencyclidine. JOHN F.

BRADY, JOON DOKKO, EMMA W. DI STEFANO, AND

ARTHURK.CHO 648

Relationship between the Murine Ah Phenotype and

the Hepatic Uptake and Metabolism of 2,3,7,8-Tetrachlorodibenzo-p-dioxin. EMILY S. SHEN AND

JAMES R. OLSON 653

The in Vitro Activity, Radioimmunoassay Cross-reac-tivity, and Molecular Weight of Thirteen RabbitCyclosporine Metabolites. N. R. HARTMAN AND I.JARDINE 661

In Vivo and in Vitro Renal Metabolism and Excretion

of Benzoic Acid by a Marine Teleost, the SouthernFlounder. MARGARET 0. JAMES AND JOHN B.PRITCHARD 665

The Disposition of N-(4,6 -Dimethyl-2-pyrimidi-nyl)benzene[U-’4C]sulfonamide in the Rat. G. D.PAULSON AND V. J. FElL 671

The Development of Hepatic Drug-metabolizing En-

zyme Activity in the Neonatal Calf and Its Effecton Drug Disposition. SUSAN E. SHOAF, WAYNE S.

SCHWARK, CHARLES L. GUARD, AND JOHN G.BABISH

The Metabolism of 7-Ethylbenz[a]anthracene by RatLiver Microsomal Preparations. S. MCKAY, P. B.FARMER, P. D. CARY, AND P. L. GROVER 682

Physiologically Based Pharmacokinetic Model for theRenal Clearance of Salicyluric Acid and the Inter-

action with Phenolsulfonphthalein in the Dog.FRANS G. M. RUSSEL, ALFONS C. WOUTERSE, AND

CEES A. M. VAN GINNEKEN

Bioactivation of Tetrachloroethylene. Role of Glutathi-

one S-Transferase-catalyzed Conjugation versusCytochrome P450-dependent Phospholipid Alkyl-ation. WOLFGANG DEKANT, GISELA MARTENS,SPYRIDON VAMVAKAS, MANFRED METZLER, AND

DIETRICH HENSCHLERGlucuronidation in Vitro and in Vivo. Comparison of

Intestinal and Hepatic Conjugation of Morphine,Naloxone, and Buprenorphine. M. MISTRY AND J.BRIAN HOUSTON

Direct Detection of New Flucytosine Metabolites in

Human Biofluids by 9F Nuclear Magnetic Reso-

nance. JEAN P. VIALANEIX, MARIE C. MALET-

MARTINO, JEAN S. HOFFMANN, JACQUES PRIS, AND

ROBERT MARTINO


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Contents (con! ‘d.)

SHORT COMMUNICATIONS M. B. BAILIE, D. A. FEDEROWICZ, K. DOLCE, C.KAHN, B. A. MICO, AND M. S. LANDI 729

Influence of Gonadal Hormones upon Rat Hepatic

Acetaminophen Sulfotransferases. ROBERT E.KANE AND LEE J. CHEN 725 Effect of Cyclosporine on Hepatic Oxidative and Con-

jugative Metabolism in Rats. RAYMOND E.Pharmacokinetics of Acetaminophen, Vancomycin, GALINSKY, DONALD P. ALEXANDER, AND MICHAEL

and Antipyrine in the Hanford Miniature Swine. R. FRANKLIN 731

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767

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857

868


November/December 1987 Vol. 15, No.6

CONTENTS

The Disposition and Pharmacokinetics of Ketocona-zole in the Rat. RORY P. REMMEL, KWAME AMOH,

ANDMAHMOUDM.ABDEL-MONEM 735

Metabolism and Disposition of Cyproheptadine and

Desmethylcyproheptadine in Pregnant and FetalRats. SAMSON A. CHOW AND LAWRENCE J.FISCHER 740

Effects of Model Traumatic Injury on Hepatic DrugMetabolism in the Rat. VI. Major Detoxification!Toxification Pathways. LANDIS K. GRIFFETH, GER-ALD M. ROSEN, AND ELMER J. RAUCKMAN 749

Metabolite Profile in Milk of Lactating Rats after Treat-ment with a Carcinogen, N-2-Fluorenylacetamide.DANUTA MALEJKA-GIGANTI, WELSONIA J. MAGAT,

ANNETrE M. ADELMANN, AND RICHARD W.DECKER

Species-dependent Enantioselective Glucuronidation ofThree 2-Arylpropionic Acids: Naproxen, Ibupro-

fen, and Benoxaprofen. MOHAMED EL MOUELHI,HANS W. RUELIUS, CATHERINE FENSELAU, AND

DEANNE M. DULIK

Pharmacokinetics and Metabolism of the AntitumorDrug Amonafide (NSC-308847) in Humans. T. B.FELDER, M. A. MCLEAN, M. L. VESTAL, K. LU, D.FARQUHAR, S. S. LEGHA, R. SHAH, AND R. A.NEWMAN

Disposition, Pharmacokinetics, and Metabolism of a

Dermal Dose of [4C]2,5-Hexanedione in Hens.

ELIZABETH SUWITA, AMIN A. NOMEIR, AND Mo-HAMED B. ABOU-DONIA 779

Monooxygenase-mediated Activation of Chlorotriani-sene (TACE) in Covalent Binding to Rat HepaticMicrosomal Proteins. MARLENE J. JUEDES, WIL-

LIAM H. BULGER, AND DAVID KUPFER 786

The Pharmacokinetics of Pentane, a By-product ofLipid Peroxidation. SANDRA R. B. ALLERHEILIGEN,

THOMAS M. LUDDEN, AND RAYMOND F. BURK .. 794

Co-oxidation of 2-Bromohydroquinone by Renal Pros-taglandin Synthase. Modulation of Prostaglandin

Synthesis by 2-Bromohydroquinone and Glutathi-one. SERRINE S. LAU AND TERRENCE J. MONKS.. 801

N-Oxidation of N-Methyl Pyrrolidine Released in Vivofrom Cefepime. S. THOMAS FORGUE, PRASAD

KARl, AND RASHMI BARBHAIYA 808

Isolation and Characterization of 4’-Hydroxy T-2Toxin, a New Metabolite of the TrichotheceneMycotoxin T-2. CATHERINE A. KNUPP, DAVID G.CORLEY, MICHAEL S. TEMPESTA, AND STEVEN P.SWANSON

Metabolism and Excretion of Dinitrobenzenes by MaleFischer-344 Rats. DEBRA D. NYSTROM AND

DOUGLAS E. RICKERT 821

Cryopreservation of Rat and Dog Hepatocytes for Stud-ies of Xenobiotic Metabolism and Activation. G.P0WIs, K. S. SANTONE, D. C. MELDER, L. THOMAS,

D. J. MOORE, AND T. J. WILKE 826

Oxidative Metabolism of Butylated Hydroxytoluene byHepatic and Pulmonary Microsomes from Rats

and Mice. JOHN A. THOMPSON, ALVIN M. MALK-

INSON, MICHAEL D. WAND, SUSAN L. MASTOVICH,

ELLIOTr W. MEAD, KATHLEEN M. SCHULLEK, AND

WADE G. LAUDENSCHLAGER

Evidence for Diazotization of ‘4C-Sulfamethazine �4-Amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-[U-’4C]sulfanomidel in Swine. G. D. PAULSON

AND V. J. FElL 841

Mechanism-based Inactivation of the Major /3-Naphthoflavone-inducible Isozyme of Rat Liver

Cytochrome P-450 by the ChloramphenicolAnalog N-(2-p-Nitrophenethyl)dichloroacetamide.

NATALIE E. MILLER AND JAMES R. HALPERT . . . . 846

Selective Inactivation by Chioramphenicol ofthe MajorPhenobarbital-inducible Isozyme of Dog Liver

Cytochrome P-450. PAUL J. CIACCIO, DAVID B.

DUIGNAN, AND JAMES R. HALPERT 852

Conversion of Bromobenzene to 3-Bromophenol. ARoute to 3- and 4-Bromophenol through Sulfur-Series Intermediates Derived from the 3,4-Oxide.K. LERTRATANANGKOON, E. C. HORNING, AND M.0. HORNING

Isolation and Identification of Major Metabolites of

Tixocortol Pivalate in Human Urine. F. CHAN-OINE, C. GRENOT, N. SELLIER, W. E. BARRET’r, R.M. THOMPSON, A. F. FENTIMAN, J. R. NIXON, R.GOYER, AND J. L. JUNIEN

Mechanism of Metabolic Cleavage of a Furan Ring.TSUTOMU KOBAYASHI, JUKO SUGIHARA, AND

SH0ICHI HARIGAYA 877


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)

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single copy $15.00 ($17.00 foreign). Prices subject to change. Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics.

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Phenolic Metabolites of Amitriptyline and Nortripty- SWYSEN, J. THIJSSEN, PH. TIMMERMAN, R. WOES-

line in Rat Bile. URSULA BREYER-PFAFF, A. PROX, TENBORGHS, AND J. HEYKANTS 905H. WACHSMUTH, AND PEIPEI YAO 882

Metabolism of (+)-trans-�8-Tetrahydrncannabinol inAmitryptyline Metabolites in Human Urine. Identifi- the Mouse in Vitro and in Vivo. D. J. HARVEY AND

cation of Phenols, Dihydrodiols, Glycols, and Ke- H. J. MARRIAGE 914tones. A. PRox AND URSULA BREYER-PFAFF 890

SHORT COMMUNICATIONS‘9F NMR Analysis of the Carbamate Reaction of a-

Fluoro-fl-alanine (FBAL), the Major Catabolite of Identification of the Etodolac Metabolite, 4-Ureido-Fluoropyrimidines. Application to FBAL Carba- etodolac, in Mouse, Rat, Dog, and Man. E. S.mate Determination in Body Fluids of Patients FERDINANDI, I). COCHRAN, AND R. GEDAMKE 921Treated with 5’-Deoxy-S-fluorouridine. R. MAR-

TINO, M. C. MALET-MARTINO, C. VIALANEIX, A. [3HjChloramphenicol Metabolism in Human Volun-

LOPEZ, AND M. BON 897 teer: Oxamic Acid as a New Major Metabolite. D.E. CORPET AND G. F. BoRws 925

Excretion and Biotransformation of Alfentanil and Su-fentanil in Rats and Dogs. W. MEULDERMANS, J. Author Index 928HENDRICKX, W. LAUWERS, R. HURKMANS, E. Subject Index 930

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Documents

Drug Metabolism and Disposition207 161 168 217 184 237 250 DRUG METABOLISM AND DISPOSITION (ISSN 0090-9556) is published bimonthly by the American Society for Pharmacology and Experimental