INDEX

(Page number shown is first page of article in which entry is indexed.)

Acetaminophen, 418 Barbiturates, breakdown of cytochrome P-450 heme Acetanilide, 418 by, 275 Acetanilide hydroxylation, 191 Benzo[a]pyrene hydroxylation by aryl hydrocarbon effect of metyrapone and analogs on, 184 hydroxylase, 386 Acetone, effects on electron paramagnetic resonance Benzpyrene hydroxylase, 380 signals, 231 Benzpyrene metabolism in control and induced rats Acetophenetidin, effect of analgesics and cigarette and mice, 380 smoke on metabolism of, 211 Biliary excretion, effects of phenobarbital in man, 424 N-acetyl-p-aminophenol, effect of analgesics and Bilirubin, effect of ethanol on, 428 cigarette smoke on metabolism from acetopheneti- Blood flow, liver, to determine drug half-lives, 411 din, 211 Active centers of hepatic microsomal cytochrome P-450, 194 Carbanions, formation and binding by cytochrome Active site of cytochrome P-450, I P-450, 176 Adjuvant-induced arthritis in rat, impaired drug Carbon disulfide, loss of cytochrome P-450 by, 267 metabolism in, 251 Carbon monoxide, 191 ah locus, association with drug-metabolizing enzymes, binding activation energies, I 231 binding rate constants, I Albumin, transfer from cytochrome P-420 in metab- effect on N-oxidation, 299 olism of cytochrome P-450, 293 production, 286 Alcohol dehydrogenase, differentiation from micro- specific carrier in lung and placenta, 374 somal ethanol-oxidizing system, 428 Carcinogen metabolism, induction in skin in tissue Alkyl hydroperoxides, 92 culture, 386 Allopurinol, inhibition of drug metabolism after, 402 Catabolism Allylisopropylacetamide, 259, 286 heme, 286 2-Allyl-2-isopropylacetamide, loss of cytochrome hemoprotein, 286 P-450 by, 267 Catalase Amines differentiation from microsomal ethanol-oxidizing individual, N-oxidation of, 299 system, 428 primary, deamination of, 337 role in hepatic microsomal ethanol oxidation, 441 Amino acyl tRNA synthetase activity, 239 Chlorinated hydrocarbons, carbanion formation by re- p-Aminobenzoic acid, 259 duction of, 176 Amino carbinol oxidation, 322 Cholestasis, effect of phenobarbital on, 424 5-Aminolevulinate synthetase activity, relation of loss Cholesterol of heme to, 267 content of lung and liver microsomes, 358 Aminolevulinic acid, 259 metabolism, effects of ethanol on, 428 Aminotriazole, 259 Cigarette smoke, effect on acetophenetidin metabolism, Amphetamine deamination, phenylacetone oxime in, 211 332 Cobaltous chloride, 259 Analgesics, effect on acetophenetidin metabolism, 211 Cortisol, to determine drug half-lives, 411 Aniline hydroxylation, 191 Cortisone acetate, effect on drug metabolism, 216 Antituberculous drugs, effect on cytochrome P-450 con- Covalent binding, 418 tent and hydroxylating enzyme system, 224 Cyanide, effects on drug oxidation, 139 Arthritis, adjuvant-induced, in rat: impaired drug Cytochrome b,, 129 metabolism in, 251 electron transfer mediated by, 150 Arylamines, N-oxidation, 314 Cytochrome P-420 Aryl hydrocarbon benzo[a]pyrene hydroxylase, 231 characterization, 45 Aryl hydrocarbon hydroxylase, induction in human differences in ‘untreated and 3-methylcholanthrene- skin in tissue culture, 386 treated rats, 40 Azo reduction, type II substrate oxidation and, en- transfer to albumin in metabolism of cytochrome hancement by metyrapone, 191 P-450, 293

483 484 IN DEX

Cytochrome P-448 Electron paramagnetic resonance, to probe spin state effect on substrate specificity, 29 of iron, 45 extinction coefficient, 29 Endocrine systems, chemistry of cytochrome P-450 phospholipid content, 29 from, 21 purification, 29 Endoplasmic reticulum, synthesis and degradation of spectrum, 29 membrane proteins in, 84 Cytochrome P-450 Endoplasmic reticulum membranes, dynamic organ- anomalous properties, 6 ization of, 66 chemistry, from endocrine systems, 21 Enzyme inducers, effect on substrate specificity, 199 destruction, drug-induced, 267 Enzyme proteins, turnover in microsomal membrane, 80 effect on substrate specificity, 29 Enzyme-substrate complex, 111 enzyme systems, mechanism, 164 Ethanol metabolism, oxidative and peroxidative extinction coefficient, 29 mechanisms, 449 free hepatic polyribosomes and, 62 Ethanol oxidation genetic differences, 231 hepatic microsomal, role of hydrogen peroxide and heme, breakdown by barbiturates, 275 catalase in, 441 hydrophobic region, 6 hepatic microsomal, significance and characteriza- mechanism of action, 92 tion, 428 molecular function, 98 NADPH-cytochrome c reductase in, 455 NADPH-cytochrome c reductase and, 121 Ethylmorphine, spectral changes, 129 N-oxidation of amines, 299 Ethylmorphine N-demethylation, effect of steroids on, optical and magnetic probes of, 45 216 oxygenated, 129 Extinction coefficient of cytochromes P-450 and P-448, partial purification, 6 29 phospholipid content, 29 Extrahepatic drug metabolism, effects of hepatic in- placental, role in oxygen diffusion, 368 ducers and inhibitors on, 342 purification, 29 Extrahepatic microsomal N-oxidation, 299 reductase, 380 Extrahepatic mono-oxygenase system, 350 solubilized, 156 spectrum, 6, 29 Flavoprotein-catalyzed N-oxidation, 314 substrate complexes, I I I Fluorene, interaction with cytochrome P-450, 176 Cytochrome P”450cam, Furosemide, 418

DDT and benzpyrene as inducers in rats and mice, 380 Deamination, microsomal, heavy isotope studies, 337 Genetic differences in cytochrome P.450, 231 Degradation of microsomal hemoproteins, 256 Glucose metabolism, effects of ethanol on, 428 Dehydrogenase, microsomal, 322 Glutathione, 418 Dehydrogenation of 2-hydroxymedazepam, 322 Glycine conjugation, 259 Desmethylimipramine metabolism, interindividual differences, 469 Heavy isotope studies of microsomal deamination, 337 Detergent(s) Heme catabolism, 286 effects on electron paramagnetic resonance signals, Heme oxygenase, 286 231 Heme synthesis, 259 treatment of microsomes, 74 Heme transfer, implication in metabolism of cyto- Diazepam, from oxidation of 2-hydroxymedazepam, chrome P-450, 293 322 Hemoglobin binding by lung microsomes, 358

3, 5-Diethoxycarbonyl-l , 4-dihydro-2 , 4 , 6-trimethyl- emolysis, 418 pyridine, 259 Heterogeneity of cytochrome P.450 in vicinity of heme, Dimethylaniline, N-oxidation of, 314 45 Dioxymethylene compounds as ligands for cytochrome Hexobarbital, spectral changes, 129 P-450, 176 Hexobarbital hydroxylation, effect of steroids on, 216 Diphenylhydantoin metabolism, interindividual dif- Hydrogen peroxide, role in hepatic microsomal ethanol ferences, 469 oxidation, 441 Disulfiram, inhibition of drug metabolism after, 402 Hydroperoxides, 92 i-Dopa, inhibition of drug metabolism after, 402 Hydrophobic region of cytochrome P-450, 6 DPNH synergism of TPNH-dependent mixed function Hydroxylase, microsomal, unspecific, induction in hu- oxidase reactions, 139 man liver, 224 Dynamic organization of endoplasmic reticulum mem- II 3-Hydroxylase of adrenocortical mitochondria, cy- branes, 66 tochrome P-450 function and, 21 INDEX 485

Hydroxylation, drug, 92 Mixed function oxidations, 129 2-Hydroxymedazepam, oxidation, 322 Molecular function of cytochrome P-450, 98 Hyperlipemia from ethanol, 428 Molecular size-turnover correlation of membrane proteins, 84 Induction of cytochrome P450 reductase by pheno- Molecular weight of solubilized cytochrome P-450, 156 barbital vs. 3-methylcholanthrene, 380 Mononuclear ferric iron, probes of spin state in oxi- Inelastic light-scattering studies of phospholipids, 74 dized cytochrome P450, 45 Inhibition of drug metabolism, 164, 402 Mono-oxygenase induction, genetic differences in cy- Inhibitors tochrome P450 during, 231 and inducers, liver and kidney cortex compared, 350 Mono-oxygenase system, rat kidney cortex, 350 effects on N-oxidation, 299 M#{246}ssbauerparameters of cytochrome P4SOcam, of drug metabolism, 162 Mutual depletion system kinetics, 194 Initiation factor activity after 3-methylcholanthrene NAD-dependent microsomal dehydrogenase, 322 and -naphthoflavone, 239 Interindividual differences NADH oxidation, relation to NADPH oxidation, ISO in drug metabolism in man, 469 NADPH, formation of microsomal hydrogen peroxide in drug oxidation in man, 411 from, 441 Ionic strength, effects on cytochrome P450 reductase, NADPH-cytochrome c reductase, 92 380 microsomal oxidation of ethanol and methanol, 455 Isosafrole, effect on extrahepatic drug metabolism, 342 role in microsomal reactions, 121 NADPH-cytochrome P-450 reductase, 92 Ligands NADPH oxidations, relation to NADH oxidation, 150 carbanions as, 176 -Naphthoflavone, initiation factor after, 239 cytochrome P’4SOcam, 2-Naphthylamine, N-oxidation of, 314 Lipid peroxidation, 286 Necrosis, liver, 418 Lung, oxygen and carbon monoxide carrier in, 374 Neoprontosil reduction, 191 Lung microsomes, relation to drug metabolism, 358 2-Nitropropane, ligand binding of, 176 Nonmercaptide ligand, variable, in oxidized hemo- M, factor, 239 protein, 45 Nonsubstrates, interaction with flavoprotein oxidase, M, + M, factor, 239 Magnetic probe of cytochrome P-450’s, 45 314 Membrane proteins, synthesis and degradation of, 84 Nortriptyline, inhibition of drug metabolism after, 402 Membranes, enzyme turnover in, 80 Nortriptiline metabolism, interindividual differences, Mercaptide ligand, fixed, in oxidized hemoprotein, 45 469 Messenger RN A-polyribosome-cytochrome P-450 com- Novaminsulfonum, effect on drug metabolism, 224 plex, 62 N-oxidation of arylamines, 314 Messenger RNA’s, effect of phenobarbital on, 248 N-oxidation of individual amines, cytochrome P.450 Metal ion effects on cytochrome P-450 reductase, 380 role, 299 Methanol oxidation, NADPH-cytochrome c reductase Optical difference spectra, 391 in, 455 Optical probe of cytochrome P-450’s 45 Methemoglobinemia, 418 Oxidative mechanisms of ethanol metabolism, 449 3-Methylcholanthrene Oxygen carrier, specific, in lung and placenta, 374 effects on electron paramagnetic resonance spectra, Oxygen diffusion, role of placental cytochrome P-450 231 in, 368 effect on extrahepatic drug metabolism, 342 Oxygen incorporation, mechanism, 299 effect on P-420 hemoproteins in rat, 40 Oxygen pressure, effects on N-oxidation, 299 initiation factor after, 239 Oxyphenbutazone oxidation, antipyrine half-life to Methylenedioxyphenyl compounds, 391 assess, 411 Methyltestosterone, effect on drug metabolism, 216 Metyrapone, 191 Particle size, 74 determiination of active centers of hepatic micro- Peroxidative mechanisms of ethanol metabolism, 449 somal cytochrome P.450, 194 pH, effect on oxidation pathways, 299 modifier of microsomal drug metabolism, 184 Phenacetin, 418 M itochondrial electron transport, 139 Phenacetin-caused spectral changes, 111 Mixed function oxidase activities and related enzymes, Phenobarbital 358 effects on biliary excretion in man, 424 Mixed function oxidase reactions, TPNH-dependent, effect on extrahepatic drug metabolism, 342 DPNH- synergism of, 139 effect on messenger RNA’s, 248 486 IN DEX

Phenylacetone oxime, intermediate in amphetamine Species differences in induction by DDT vs. benzpyrene, deamination, 332 380 Phenylbutazone oxidation, antipyrine half-life to as- Spectral changes, 111 sess, 411 in cytochrome P450 after 3-methylcholanthrene Phospholipase C digestion, effect on lung and liver treatment, 40 mixed function oxidase activities, 358 Spironolactone, effect on drug metabolism, 216 Phospholipid, role in microsomal hydroxylations, 156 Stearoyl-CoA, effects on drug oxidation, 139 Phospholipid content Steroids, effect on rat drug metabolism, 216 of cytochromes P-450 and P448, 29 Stoichiometry of oxygen reduction, 98 of lung and liver microsomes, 358 Substrate binding Phospholipid exchange in microsomal membrane, 74 effects on electron paramagnetic resonance signals, Piperonyl butoxide, 391 231 effect on extrahepatic drug metabolism, 342 to cytochrome P450, effect of phospholipid on, 156 Placenta, oxygen and carbon monoxide carrier in, 374 Substrate-induced difference spectra, lung and liver, Placental cytochrome P450, role in oxygen diffusion, 358 368 Substrate interaction, Ill Polyribosomes, free hepatic, associated with cyto- with cytochrome P450, 98 chrome P-450, 62 Substrate specificity

Polyuridylic acid-directed 14 C-phenylalanine in- effect of cytochromes P450 and P-448 on, 29 corporation, 239 effect of enzyme inducers on, 199 Porphyria, 259 liver and kidney cortex compared, 350 experimental, 286 Superoxide, 92 experimental, induced by allylisopropylacetamide and Synergists, effect on drug metabolism, 391 related compounds, 275 Synthesis of microsomal hemoproteins, 256 Porphyrin, effect of ethanol on, 428 Prazepam, inhibition of drug metabolism after, 402 Temperature changes, effects on electron paramag- Pseudomonas putida cytochrome P-450, 14 netic resonance signals, 231 Tetrahydrocannabinol Reconstituted mixed function oxidase system, 156 inhibition of drug metabolism after, 402 Reduced pyridine nucleotides, 98 metabolism in man, 461 Reticuloendothelial cells, spleen and liver, in metab- metabolite disposition, 461 olism of cytochrome P450, 293 Toxic metabolites, 418 Reverse type I spectral change, Ill TPNH-dependent mixed function oxidase reactions, Rifampicin, effect on cytochrome P-450 content and DPNH synergism of, 139 hydroxylating enzyme system, 224 Turnover of microsomal membrane proteins, 80 RNA content of lung and liver microsomes, 358 Comparison in vivo and in vitro, 87 Type I drugs, 139 Sedimentation of resolved cytochrome P-450, 156 Type II drugs, 139 Skin, human, aryl hydrocarbon hydroxylase induction Type II substrate oxidation and azo reduction, en- in cultures of, 386 hancement by metyrapone, 191 Smooth endoplasmic reticulum, proliferation, 428 Type III difference spectrum, 391 DRUG METABOLISM AND DisPosmoN Vol. 1 No. 6 Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A.

AUTHOR INDEX

Alvares, A. P., 386 Edelson, J., 737 Anders, M. W., 293, 642, 659 Eisenbrandt, L. L., 523

Anderson, D. J., 691 Ellin, A., 350 Arison, B. H., 721 Erickson, R. R., 74 Aurori, K. C., 669 Ernster, L., 66 Autor, A. P., 156 Estabrook, R. W., 98, 129, 350 Evans, G. H., 679 Baker, R. C., 391 Baron, J., 98, 121, 129 Farquhar, D., 580 Beck, F. J., 251 Fleischmann, R. A., 224 Bend, J. R., 358 Fouts, J. R., 380 Bloomfield, V. A., 74 Blumberg, W. E., 45 Gabriel, T. F., 557 Bower, R. J., 721 Garteiz, D. A., 565 Boyer, R. F., 92 Gerber, N., 489 Branch, R. A., 679, 687 Gillespie, D. D., 211 Breckenridge, A., 411 Gillette, J. R., 150, 164, 216, 418 Bresnick, E., 239 Glazko, A. J., 711 Bridges, J. W., 342 G#{243}gl,A., 424 Brodie, B. B., 418 Gottlieb, J. A., 645, 756 Burns, B., 368, 374 Gram, T. E., 74, 358 Griffin, B. W., 14 Carter, E. A., 449 Gunsalus, I. C., I Casmer, C., 611 Gurtner, G. H., 368, 374 Castle, M. C., 590 Cavallito, J., 211 Hamrick, M. E., 216 Cha, Y.-N., 516 Harvey, D. J., 569 Chabner, B. A., 580 Hasegawa, E., 259 Chakraborty, J., 342 Heidema, J. K., 156 Chando, T. J., 619 Hildebrandt, A. G., 129, 194 Chang, R., 611 Hill, R. M., 569 Cinti, D. L., 111, 350, 516 Ho, D. H. W., 752 Cohen, A. I., 619 Hodgson, E., 391 Conney, A. H., 199, 386, 766 Holtzman, J. L., 74 Considine, N., 231 Hook, G. E. R., 358 Coon, M. J., 92, 156 Hopkins, R., 342 Cooper, D. Y., 21 Horning, M. G., 569 Cooper, M. J., 642, 659 Horv#{225}th,T., 424 Correia, M. A., 139 Hucker, H. B., 332, 721 Cunningham, R. F., 742 Husain, S., 523

Davies, D. S., 411 Dayton, P. G., 742 Ichikawa, Y., 62 Imai, Y., 6 DeCarli, L. M., 428 Deckert, F. W., 704 Isaacson, E. L., 121 Dehlinger, P. J., 84 Israili, Z. H., 742 Isselbacher, K. J., 449 De Matteis, F., 267 Desiderio, D. M., 489 Dewan, R. K., 74 Jacobson, M., 199, 275, 766 Di Carlo, F. J., 530 Jakobsson, S. V., 350 Dice, J. F., 84 J#{225}vor,T., 424 Douglas, J. F., 737 Johns, D. G., 580 Drayer, D. E., 577 Johnson, A. 0., 669 Duppel, W., 156 Jollow, D. J., 418

787 788 AUTHOR INDEX

Kahe, G. F., 191 Nies, A. S., 679, 687 Kappas, A., 386 Nowlin, J., 569 Kaschnitz, R. M., 156 Khaliq, A., 756 Omura, T., 80, 248 Kimmel, H. B., 537 Orme, M., 411 Knapp, W. C., 565 Orrenius, S., 66, 111, 350 Kniffen, F., 259 Ortiz, E., 184, 543, 775 Kohl, K. B., 455 Kolis, S. J., 322, 557 Parke, D. V. W., 342 Kon,H., 231 Parli, C. J., 337, 628 Kuntzman, R., 199, 275, 766 Passananti, G. T., 402 Kupfer, D., 760 Peisach, J., 45 Perel, J. M., 742 Lage, G. L., 590 Peterson, J. A., 14, 129 Lake, B. G., 342 Philpot, R. M., 391 Lan, S. J., 619 Pieper, W. A., 634 Lanclos, K. D., 239 Piper, W., 259 Lee, N. W., 628 Poulsen, L. L., 314 Leeson, G. A., 565 Leibman, K. C., 184, 543, 775 Reidenberg, M. M., 577 Leigh, S., 386 Remmer, H., 224 Lemberger, L., 46! Rhodes, R. E., 721 Le Page, G. A., 756 Roots, I., 194 Levin, W., 29, 199, 275, 386, 766 Rosenfeld, J., 760 Lewis, D. D., 530 Rosenthal, 0., 21 Lieber, C. S., 428 Ruelius, H. W., 537 Lin, C., 611 Ryan, D., 29, 199 Lipscomb, J. D., I Liu, A. L., 537 Sasame, H. A., 150, 164 Loo, T. L., 580, 645 Satake, H., 6 Lu, A. Y. H., 29, 199,766 Sato, R., 6 Lu, K., 645 Schacter, B. A., 121, 286 Ludwig, B. J., 737 Schenkman, J. B., 111, 350, 516 Schimke, R. T., 84 Mailman, R. B., 391 Schleyer, H., 21 Maines, M. D., 293 Schmid, R., 256 Mannering, G. J., 40, 139, 663 Schnabel, K. H., 176 Marver, H. S., 286 Schoene, B., 224 Mason, H. S., 62 Scholz, R., 441 Mason, J. I., 98 Schreiber, E. C., 619 Masters, B. S. S., 121, 455 Schwartz, M. A.. 322, 557 Matsubara, T., 98 Scott, K. N., 506 Matsumura, S., 248 Segaloff, A., 537 McKee, E. M., 314 Seibert, R. A., 489 McMahon, F. G., 721 Sernatinger, E., 275 McMahon, R. E., 337, 628 Shand, D. G., 679, 687 Menard, R. H., 216 Shoeman, D. W., 40 Merits, I., 691 Sisenwine, S. F., 537 Meyer, U. A., 286 Sitar, D. S., 663 Minck, K., 191 Sj#{246}qvist,F., 469 Mirkin, B. L., 659 Skeen, M. 3., 634 Mitchell, J. R., 150, 418 Somogyi, A., 199 Mitoma, C., 698 Sonders, R. C., 691 Moldeus, P., 111, 516 Stauffer, S. C., 721 Stern, J. 0., 45 Nebert, D. W., 231 Stratton, C., 569 Negishi, M., 80 Stripp, B., 164, 216 Nelson, E. B., 121, 455 Strobe!, H. W., 92 Netter, K. J., 162, 191 Symchowicz, S., 611 AUTHOR INDEX 789

Takemori, A. E., 642 Waddell, W. J., 598 Taylor, J. M., 84 Webb, C., 259 T#{233}nyi,1., 424 Weiner, I. M., 742 Tephly, T. R., 259 Welch, R. M., 211 Thompson, R. M., 489 Weliky, I., 619 Thor, H., 350 Werringloer, J., 98 Thorgeirsson, S. S., 150, 4!! West, S. B., 29, 199 Thurman, R. 0., 44! White, S. D., 721 Toome, V., 557 Whitehouse, M. W., 251 Trussler, P., 259 Wilder, B. J., 506 Wilkinson, 0. R., 679 Uehleke, H., 299 Williams, C. M., 506 Ullrich, V., 176 Williams, T. H., 557 Umbenhauer, E. R., 721 Wolpert, M. K., 580 Wosilait, W. D., 523 Valerino, D. M., 669 Wright, 0. J., 565 van der Hoeven, T. A., 156 Vane, F. M., 40 Zampaglione, N. 0., 216 Vese!l, E. S., 402, 669 Ziegler, D. M., 314 von Bahr, C., 469 Zuleski, F. R., 530 DRUG METABOLISM AND DlsPosmoN Vol. 1 No. 6 Copyright 0 1973 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A.

SUBJECT INDEX*

Acetanilide gas, analysis of permethylated rat bile by, 489 p-hydroxylation, inhibition, 775 liquid, high-speed, of cephalothin and deacetyl- metabolic rate, 766 cephalothin, in man, 659 N-Alanyldopamine-’4C, metabolism, species differ- Contraceptive, oral, disposition, in rat, 530 ences, 691 Cuprex, toxicity, in man, 577 Aldehyde oxidase, synthesis and interaction of dialkyl Current Literature, 552, 606, 653, 715, 780 esters with, 580 1-(2-Cyanophenyl)imidazole, as inhibitor of drug Aminopyrine, N-demethylation, inhibition, 775 metabolism, 775 Amobarbital, hydroxylation, 663 02, 2’-Cyclocytidine, metabolism, 752 Aniline, p-hydroxylation, inhibition, 775 Cytochrome P.420, extinction coefficients, 516 Aniline hydroxylase, effect of centrally active drugs Cytochrome P448, n-octylamine difference spectra, on, 669 in rat and mice, 602 Anticoagulants, metabolism, 704 Cytochrome P450 9-$-D-Arabinofuranosyladenosine, in man, 756 binding of barbiturates to, 663 1-j9-D -Arabinofuranosy!cytosine, 02,2’ -cyclocytidine effect of centrally active drugs on, 669 as a depot form of, 752 extinction coefficients, 516 9-$-D-Arabinofuranosylhypoxanthine, in man, 756 heme degradation, role in pentobarbital and acet- Arabinosy!-6-mercaptopurine, metabolism and dis- anilide metabolism, 766 position, 645 n-octylamine difference spectra in rat and mice, 602 1-Ary!imidazo!es, as inhibitors of drug metabolism, solubilization, 516 775

Assay, radioactive, for hexobarbital hydroxylase in Deacety!cephalothin, ion-pair extraction and liquid liver microsomes, 760 chromatography, in man, 659 Dialkyl esters, methotrexate and 3’, 5’-dichloro- Barbiturates, metabolism, 663 methotrexate, 580 Bile, rat, identification of metabolites in, 489 Diazepam, effect, on liver microsoma! enzymes, 669

Biliary excretion, 14C-dicumarol, in rat, 523 3’ , 5’-Dichloromethotrexate Blocking agent, 9-receptor, in dog, 565 dialkyl esters, 580 Blood flow, liver, effects on propanolol disposition, 687 7-hydroxy-, 580 Bornanediones, reduction, 543 2 ,4-Dichloro-6-phenylphenoxyethy!amine, metabo- Borneols, stereospecific formation from D- and L- lism, relationship with activity as mono-oxy- camphor, 543 genase inhibitor, 628 ‘4C-Dicumarol, biliary excretion, in rat, 523 Camphor, reduction and hydroxylation, 543 3H-Digitoxin, excretion, effect of spironolactone on, Cephalothin, ion-pair extraction and liquid chroma- in rat, 590 tography, in man, 659 Dihydrofolate reductase, synthesis and interaction of Chlorocyclizine, N-demethylation, 766 dialkyl esters with, 580 Chlorocyclizine-”C, distribution, in mice, 598 4-[3- (Dimethylamino)propylj-3 ,4-dihydro-2- (1 -hy- 2 -Chloro-6 -phenylphenoxyethylamine, metabolism, droxyethyl) -3 -phenyl-2H- 1, 4-benzothiazine, relationship with activity as mono-oxygenase metabolism, in rat, dog, and monkey, 619 inhibitor, 628 Diphenylhydantoin Chlorpromazine, effect, on liver microsomal enzymes, effect, on liver microsomal enzymes, 669 669 metabolism, 711 5-Chlorosalicylic acid, binding and disappearance, in Dopamine-’4C, metabolism, species differences, 691 rat and dog, 737 Chromatography Editorial, 487 anion exchange, high pressure, 663 Elimination rate, ethanol, in chimpanzee and mon-

* The subject index for ‘The Second International Sym- key, 634 Enantiomers posium on Microsomes and Drug Oxidations” is found in Drug Metabolism and Disposition 1: 483-486 (January! metabolism, microsomal, 642 February), 1973. The author index for the January/Feb- substrate binding, 642 ruary issue is included in the author index presented on Ethanol p. 787. effect

790 SUBJECT INDEX 791

on ethanol elimination rate in chimpanzee and Mass spectrometry rhesus monkey, 634 chemical ionization, 506 on liver microsomal enzymes, 669 electron impact, 506 elimination rate, in chimpanzee and rhesus monkey, identification of glucuronides in rat bile by, 489

634 Mass spectroscopy, characterization of l-methyl-(2 , 6- Ethosuximide, metabolism, in rat and man, 569 xylyloxy)ethylamine metabolites by, 506 2-Ethyl-2-methylsuccinimide, metabolism, in rat and Meprobamate, effect, on liver microsomal enzymes, man, 569 669 Ethylmorphine N-demethylase, effect of centrally ac- Methotrexate tive drugs on, 669 dialkyl esters, 580 Excretion, fecal, of digitoxin metabolites in rat, 590 7-hydroxy-, 580 N-Methylation, pathway for oxprenolol metabolism, cis-5-Fluoro-2-methyl- 1 - [p- (methylsulfinyl) -benzyli- in dog, 565 denylj-indene-3-acetic acid, disposition and 3-Methylcholanthrene, effects metabolism, species differences, 721 on O-demethylation of griseofulvin in rat and mice, 611 Glucuronides on n-octylamine-cytochrome P450 difference identification by mass spectrometry in rat bile, 489 spectra interaction, 602

monohydroxyethosuximide, 569 1-Methyl-(2 , 6-xylyloxy)ethylamine metabolites, char- Griseofulvin acterization, 506 effect, on O-demethylation of griseofulvin, in rat Monohydroxyethosuximide metabolites, in rat and and mice, 611 man, 569 metabolism, in rat and mice, 611 Nuclear magnetic resonance Hexobarbital hydroxylation, 663 “C and ‘H, characterization of I-methyl-(2,6- in liver microsomes, 760 xylyloxy)ethylamine metabolites by, 506 18-Homoestriol metabolic disposition, species dif- Fourier transform, 506 ferences, 537 Hydroxycamphors, oxidation, 543 iz-Octylamine, difference spectra of cytochromes P450 Hydroxylation and P448, in rat and mice, 602 barbiturates, 663 Oxprenolol, metabolism, in dog, 565 ring, lack, in metabolism of probenecid, 742 warfarin, in guinea pig, 704 Pentobarbital 2-Hydroxynicotinic acid, biotransformation, 557 hydroxylation, 663 Hypoprothrombinemia, produced by warfarin and metabolic rate, 766 metabolites, 704 Permethylation, rat bile, identification of metabolites in, 489 Inhibitors, mono-oxygenase, 628 Phenobarbital, effects Ion-pair extraction, of cephalothin and deacetylcepha- on O-demethylation of griseofulvin in rat and mice, lothin, in man, 659 611 1-(2-Isopropylphenyl)imidazole, as inhibitor of drug on liver microsomal enzymes, 669 metabolism, 775 Probenecid, metabolites and analogs, 742 Propanolol, disposition, 679, 687 L12l0 leukemia cells, metabolism of 02, 2’-cyclocyti- dine in, 752 Quingestanol acetate, disposition, in rat, 530 Lipid peroxidation, role, in pentobarbital and acetan- ilide metabolism, 766 Liver microsomes N-Riboside, formation in vivo, 557 Ribosyl-6-mercaptopurine, metabolism and disposi- 0-demethylation of griseofulvin by, in rat and mice, 611 tion, 645 enzymes, effects of various drugs on, 669 extinction coefficients of hemoproteins in, 516 Seclazone, biotransformation, binding, and disappear- hydroxylation of barbiturates by, 663 ance, in rat and dog, 737 metabolism SKF 525-A, effect, on propanolol disposition, 679 kinetics, 642 Spironolactone, effect, on ‘H-digitoxin excretion in of drugs, modifiers, 775 rat, 590 of pentobarbital and acetanilide, rate, 766 SQ 11,579, metabolism, in rat, dog, and monkey, 619 of SQ 11,579, in rat, dog, and monkey, 619 Stereochemistry, effect, on drug metabolism, 642 oxidation of hexobarbital by, 760 Steroids, disposition, in rat, 530 792 SUBJECT INDEX

Terpenoids, metabolism, mammalian, 543 Thiamine, plasma and tissue levels, 698 Tetrahydrofurfuryl mercaptan, metabolite of thiamifle Thiamine tetrahydrofurfuryl disulfide, absorption and tetrahydrofurfuryl disuffide, 698 disposition, in dog and man, 698 Tetralin Thiopurines, metabolism and disposition, 645 metabolism, in man, 577 toxicity, in man, 577 Warfarin, metabolism, in guinea pig, 704

M944f3’5