AUTHOR INDEX

Achkar, Charles C., 451 Buters, Joroen T. M., 688 Denissen, Jon F., 880 Grabowski, Brian A., 880 Adedoyin, Adedayo, 161 Depuy, Betsy, 139 Granero, Luis, 447 Adusumalli, Vidyasagar E., 168 Caldwell, John, 616 Deschamps de Paillette, Evelyne, Granvil, Camille P., 165 Carde, Patrice, 843 Agostini, 0., 259 843 Gray, Kevin, 371 Carter, John P., 43 Alary, J., 578 Devinsky, Orrin, 168 Gray, M. R., 36, 530 Cepa, Steven, 880 Alton, Kevin B., 866 Diamond, Sharon, 65 Green, Mitchell D., 799 Cepa, Steven P., 788 Amann, Marianne 1., 788 Dich, John, 433 Gregus, Z., 725 Chabard, Jean Louis, 637 Amin, Raju D., 139 Doll, Mark A., 371 Griffin, G. P., 969 Chan, Tze-Ming, 866 Anders, M. W., 143, 443, 51 1, 973 Doss, George A., 625, 651 Grognet, Jean-Marc, 843 Chang, Thomas K. H., 673 Anderson, Lucy M., 43 Dow, James, 738 Grubb, M. F., 709 Charkowski, D. M., 713 Ardouin, Thierry, 843 Dreifuss, Fritz E., 168 Grunnet, Niels, 433 Charman, William N., 770 Arison, Byron H., 200 Driver, Craig L, 43 Gudas, Lorraine J., 451 Chauret, N., 969 Arneric, Stephen P., 788 Dulery, Bertrand D., 738 Guenthner, Thomas M., 731 Chen, Chieh-Fu, 518 Duncan, C. A., 631 Chen, Haiyan, 673 Duncan, Carol A., 139 Haberer, Lynda J., 113 Babu, Satram R., 922 Chen, 1-wu, 400, 693 Dunnick, June K., 14 Haegele, Klaus, D., 738 Bading J. R., 643 Chen, Laishun, 566 Dwyer, Lynn M., 281 Haegele, Klaus D., 738 Bai, Stephen A., 776 Chen, Qi, 318 Hall, Stephen D., 975 Bailey, G. S., 383, 392 Chenery, R. J., 124, 189 Hamilton, Thomas C., 835 East, P., 124, 189 Baillie, Thomas A., 544, 554 Cheng, Haiyung, 139 Hamman, Mitchell A., 975 Eckhoff, Christian, 154 Baker, G. B., 756 Cheng, Xiaoqin, 206, 820 Hanano, Manabu, 50 Egorin, Merrill J., 254 Balani, Suresh K., 200, 281 Chesa-Jim#{233}nez,Jesus, 447 Hanson, Glen, 233 Ehlers, Katharine, 928 Baldeck, J.-P., 269 Chikhale, Prashant J., 592 Hara, Ken’ichi, 377, 916 Eisenhardt, E. U., 26, 31 Baradat, M., 578 Chiu, S. H. Lee, 811 Hardwick, James P., 688 Eisman, Mark S., 443 Barnes, Evelyn R., 14 Chiu, Shuet-Hing Lee, 65 1, 659 Hargreaves, Martin B., 806 Elmazar, Mohamed M. A., 928 Barnen, Jeffrey L., 947 Chollet, Philippe, 637 Harrell, A. W., 124, 189 Erkmen, Kadir, 254 Batist, Gerald, 165 Chou, Cheng-Jen, 518 Harrington, George W., 43 Ezan, Eric, 843 Baudry, Jean Paul, 637 Chow, Hsiao-Hui, 406 Harris, T. M., 392 Bayne, William F., 139 Christ, David D., 65 Hasegawa, Takaaki, 8, 561 Faiman, Morris D., 324 Bednarski, Patrick J., 419 Christensen, S. Br#{248}gger,433 Hasegawa, Takuro, 377, 916 Farmer, Peter B., 616 Bekersky, Ihor, 233 Clarke, S. E., 124, 189 Hasegawa, Yoshinari, 601 Faught, Edward, 168 Benet, Leslie Z., 85 Clement, Bernd, 486 Hashizaki, Maii, 815 Faux, S. P., 180 Bentel, Jacqueline M., 451 Coddington, Arthur B., 903 Hata, Shunsuke, 377, 916 Ferguson, Ronald J., 371 Benvenuto, J. A., 428 Coffman, B., 713 Hazard, III, E. Starr, 177 Ferrero, James L., 788 Bickel, M. H., 26, 31 Colby, Howard D., 903 Hem, David W., 371 Findlay, John W. A., 14 Bickel, Ulrich, 99 Cole,C.A., 171,304 Heitz, F., 269 Finley, Brent L., 522 Bindra, Dilbir S., 438 Colletti, Adria E., 183, 625 Heldrich, Frederick J., 177 Finn, R. D., 643 Birner, Gerbard, 143 Collins, Jerry M., 254 Henderson, L., 211 Fischer, V., 269 Boelsterli, Urs A., 956 Colson, K. E., 171 Hendrickx, Jan, 129 Fitzgerald, Michael, 788 Bolaji, 0. 0., 756 Colson, K. L., 304 Heykants, Joseph, 129 Fong, Kei-Lai L., 90 Bonacchi, 0., 259 Combes, R. D., 180 Heyn, Heleen, 443, 973 Forkert, P. Gek, 248 Bonner, Heather S., 895 Coppini, G., 259 Hijioka, Taizo, 680 French, Jacqueline, 168 Boom, Sandra P. A., 148 Couus, R. T., 36, 530, 756 Hill, Barbara A., 503 Fuentes, A., 428 Boppana, Venkata K., 90 Covey, J. M., 428 Hill, Preston, 880 Fujimaki, Masayoshi, 700 Borchardt, Ronald T., 592 Cravedi, J. P., 578 Hinojosa, Lara M., 503 Fukuyama, Takako, 479 Bories, G., 578 Crawford, Kim, 849 Hirata, Kanako, 889 Bork, V., 298 Crawford, Steven T., 537 Hirayama, Masashi, 601 Gal, Boue, Hubert, 544 Cribb, A. E., 969 Joseph, 719 Hirobe, Masaaki, 761 Bourgeois, Blaise, 168 Crysler, Carl S., 90 Garbow, J. R., 298 Hjortkjaer, Rolf K., 289 Boyd, Steven A., 880 Cui, Donghui, 544 Gargas, Michael L., 522 Hoffman, Jacob M., 200 Boylan, John F., 451 Curry, Stephen H., 443 Garland, W. A., 211 Hollenberg, Paul F., 343 Bracke, Johan, 129 Cussac, Catherine, 637 Garvey, David S., 788 Hooper, Wayne D., 719 George, Malcolm C., 352 Branch, Robert A., 161 Cyr, Terry, 849 Horeck, J., 338 Brennan, James M., 835 Gescher, Andreas, 806 Horton, Tonya L., 120 Brewer, C. Fred, 412 Dalgaard, Lars, 289 Gietl Bankmann, Yvonne, 973 Hosokawa, Masakiyo, 889 Brewer, Thomas G., 358 Danielson, Terry J., 106 Gilbert, John D., 139 Hosokawa, Shin, 909 Brouwer, Kim L. R., 120, 224 Darbyshire, John F., 584 Gillette, James R., 584 Huang, S.-M., 709 Brown, Darrel Q., 895 Darling, Inger M., 318 Gimeno, Maria Jos#{233},447 Hultin, Theresa A., 175 Brown, Lariy D., 358 Davis, Bernard B., 922 Ginos, J., 643 Huskey, Su-Er W., 651, 659 Brown, Ronald P., 858 Davis, Charles B., 90 Godeneche, Denise, 637 Hussain, M. Delwar, 36, 530 Debrauwer, L., 578 Mark E., 200 Bruckner, James V., 858 Goldman, Hutchaleelaha, Athiwat. 406 Bruelisauer, A., 194 Dehal, Shangara S., 937 Golsteyn, Lorraine R., 106 Burak, Eric S., 43 Dekant, Wolfgang, 143, 5 1 1, 667 Gombar, Charles T., 43 Iba, Kazuhiko, 294 Burcham, D. L., 709 deLuna, Florencia A., 400 Gonzalez, Frank J., 688 Iga, Tatsuji, 2, 21, 50 Burnette, Thimysta C., 55, 60 de Miranda, Paulo, 55, 60 Goto, Moritaka, 680 lnaba, T., 367 980 AUTHOR INDEX 981

Inaba, Tadanobu, 849 Labarre, Pierre, 637 Moneti, G., 259 Pond, Susan M., 139 Irshaid, Yacoub, 161 Lacreta, Frank P., 835 Mong. Seymour, 233 Pool, William F., 719 Ishii, Yasuyuki, 79 Lakshmi, Vijaya M., 922 Monks, Terrence J., 503 Pramanik, Birendra N., 866 Isnard, Francoise, 843 Lam, Gilbert N., 65 Monro, A. M., 341 Prueksaritanont, Thomayant, 85, Ito, Kiyomi, 50 Lankford, Susan M., 776 Moons, Miek M., 148 281 Larson, S. M., 643 Morris, Marilyn E., 318 PuhI, R. James, 233 Jackson, Barbara J., 827 Lau, Serrine S., 503 Mounetou, Emmanuelle, 637 Lauwers, William, 129 Mukoyama, Hiroko, 79 Qiao, G. L., 459 Jamis-Dow, Carlos A., 254 Lavrijsen, Karel, 129 Quon, C. Y., 709 Janssen, Cor, I 29 Lee, Charis, 962 Nabeshima, Toshitaka, 8, 561 Jensen, B. K., 211 Le Jeune, Ludo, 129 Nadai, Masayuki, 8, 561 Raberger, G., 338 Johnson, Marianne K., 880 Le Kerneau, Joel, 843 Nagata, Kiyoshi, 584 Rakestraw, Dariel, 65 Jones, Barry C., 806 Lemaire, M., 194 Nagata, Osamu, 761 Ramjit, Harri G., 200,903 Joseph, Gerald L., 90 Lepage, Francis, 544, 554 Nakagawa, Terumichi, 479 Rapp, Maryse, 637 Juchau, Mont R., 331 Levine, Barry S., 498 Nakatsuka, Iwao, 294 Rashed, Mohamed, 544 Jung, Frank, 486 Levine, Walter G., 412 Namkung, Moses J., 331 Redza, Zahrein M., 248 Jurima-Romet, Malle, 849 Levy, Ren#{233}H., 544, 554 Narimatsu, Shizuo, 909 Regnier, B., 289 Li, Yan, 566 Nau, Heinz, 154, 928 Reuie, Allan E., 975 K#{225}llay,Z., 338 Lin, Jiunn H., 400, 693 Nelson, Wendel L., 237 Rhodes, Gerald R., 90 Kamada, T., 367 Liu, Lida, 139 Newman, R. A., 428 Ridley, W. P., 298 Kamin, Marc, 168 Liu, Y., 725 Nicoll-Griffith, D. A., 969 Rifkind, Arleen B., 962 Kanekal, Sarathchandra, 74 Logsdon, Daniel L., 43 Nielsen, Malene S., 433 Ring, Barbara J., 352 Kang, Young-Sook, 99 Loizou, George D., 511 Nordholm, Lars, 289 Rios,G., 713 Karanam, B. V., 811 Los, Layne E., 903 Norton, Robin L., 522 Rivera, Maria I., 503 Kato, Hideo, 761 Lotze, Michael, 161 Riviere, J. E., 459 Kato, Katsuyoshi, 8 Lown, Kenneth S., 947 Oatis, Jr., John E., 177 Rodrigues, A. David, 788 Kato, Nobuo, 8 Luke, 0. M., 304 O’Brien, Julie A., 200 Rogers, J. Douglas, 139 Kauffman, Frederick C., 680 Luo, Gang, 731 O’Dwyer, Peter J., 835 Rooney, Clarence S., 200 Kauffman, Laura R., 200 Ohata, Yuka, 479 Rosenfeld, William, 168 Kawai, R., 194 Machinist, Joseph M., 788 Ohmori, Shigeru, 909 Ross, David, 206, 820 Kawamori, R., 367 Macia, Richard A., 90 Ohshima, Natsuo, 21 Rotert, Gary A., 788 Kawazoe, Sadahiro, 750 Madan, Ajay, 324 Ohta, Shigeru, 761 Rozman, P., 725 Kehrer, James P., 74 Madelmont, Jean Claude, 637 Ohtani, Michiteru, 2 Rubio, F., 211 Kemeny, N. E., 643 Madhu, C., 725 Ohtawa, Masakatsu, 79 Rushmore, T. H., 969 Kenmochi, Toshie, 916 Magdalou, Jacques, 659 Oide, Hiosumi, 680 Russel, Frans G. M., 148 Kerns,E.H., 171,304 Magee, Peter N., 43 Oinhart, Igor, 820 Rustan, Timothy D., 371 Mahadevan, S., 269 Kerssebaum, Rainer, 667 Okudaira, Noriko, 85 Ruth, James A., 206, 820 Mammarella, Martha L., 318 Khetarpal, Vinod K., 216 Olah, Timothy V., 139,200 Manabe, Tatsuo, 601 Sandberg, Jennifer A., 154 Khokhar, Abdul R., 312 Olsen, Carl E., 433 Mangold, James B., 873 Omata, Yoshiaki, Sanders, Ruth A., 537 Kido, Yuichiro, 312 688 Mangos, Steve, 248 O’Neil, James, 65 Sarkar, Mohamadi A., 827 Kim, Chin, 858 Maniglier-Poulet, Christophe, 206, Otto, Angela M., 419 Sass, JOm Oliver, 928 Kim, H. J., 725 820 Oturu, Eyitayo M., 799 Satoh, Tetsuo, 889 Kirkman, Sandra K., 175 Mannens, Geert, 129 Ouzzine, Mohamed, 659 Sawada, Yasufumi, 2, 21, 50 Kishimoto, M., 367 Mannering, Gilbert J., 663 Ozols, Robert F., 835 Saxton, P. L., 709 Kitada, Mitsukazu, 909 Manning, Randall 0., 858 Scatina, JoAnn, 175 Kitareewan, Sutisak, 607 Manzini, S., 259 Pan, Y., 298 Schaefer, J., 298 Klaassen, C. D., 725 Marathe, Punit H., 237 Pardridge, William M., 99 Scher, Howard I., 451 Klecker, Raymond W., 254 Marino, Mark T., 358 Park, Sang S., 248 Schoen, William R., 651 Kolars, Joseph C., 947 Markham, Peter M., 216 Parker, Robert J., 254 Schran, Horst F., 873 Korzekwa, Kenneth R., 688 Maskasame, Chaiyasit, 776 Parli, C. John, 352 Schwartz, Michael S., 139 Koseniauskas, Raymond, 43 Masubuchi, Yasuhiro, 909 Paroli, Leonard, 962 Scott, Dennis 0., 438 K#{246}ster,Uta, 667 Maurizis, Jean Claude, 637 Patel, Nita, 143 Semple, Hugh A., 822 Kotaki, Hajime, 2, 21 Mayersohn, Michael, 406 Patten, Chris J., 566 Shaw, Leslie M., 895 Kratochwil, Nicole A., 419 Mayol, R. F., 171, 304 Paustenbach, Dennis J., 522 Shen, Danny D., 237 Krejcy, K.. 338 McCarthy, Dennis J., 443 Peggins, James 0., 358 Shen, Ting-liang, 343 Kretz-Rommel, Anke, 956 McLellan, L. I., 392 Peris, Jos#{233}Esteban, 447 Shoeman, Janice A., 663 Krieter, Philip A., 183, 625 McQuade, R. D., 713 Perotti, Beatrice Y. T., 85 Siddik, Zahid H., 312 Kucharczyk, Norbert, 168 Meuldermans, Willem, 129 Pieraccini, P., 259 Siest, Gerard, 659 Kuemmerle, Steven C., 343 Miller, Jr., Wilson H., 451 Piotrovskij, V. K., 338 Sigurdson, E. R., 643 Kumar, Gondi N., 177 Miller, Randall R., 625, 651 Piriou, Fran#{231}ois,738 Slikker, Jr., William, I 54 Kunze, Kent L., 688, 947 Mine, Takeshi, 294 Piriou, Fran#{231}ois,738 Smith, Dennis A., 806 Kupfer, David, 937 Minery, P., 269 Pitzenberger, Steven M., 200, 903 Sofia, R. Duane, 168 Kurihara, Atsushi, 601 Misslin, P., 194 Pochopin, Nancy L., 770 Speerschneider, Petra, 667 Kuzniecky, Rueben I., 168 Mizutani, Tamio, 750, 815 Pollack,GaryM., 113, 120 Spencer, Anne P., 120 982 AUTHOR INDEX

Sperling, Michael, 168 Taylor, Wesley G., 106 Urbanski, James J., 90 Wittfoht, Werner, 928 Spielberg, S. P., 969 Tebbett, Ian R., 498 Urquhart, Michael R., 358 Wittmann, Harald, 667 Spooner, Roy W., 106 Tedford, C. E., 713 Wolf, Evelyne, 738 Stein, Herman, 880 Tephly, T. R., 713 Vage, Chandravathi, 572 Wong, Y. N., 709 Stella, Valentino J., 438, 770 Tephly, Thomas R., 799 Vandenbranden, Mark, 975 Woolf, Thomas F., 719 Stevens, Ruth, 254 Thai,GeraldW., 312 Vanrollins, M., 713 Wrighton, Steven, 975 Stresser, D. M., 383, 392 Theoharides, Anthony D., 281 Varga, Sandor L., 200 Wrighton, Steven A., 352, 947 Veyre, Annie, 637 Styczynski, P., 713 Thomas, Francois, 843 Vickers, A., 269 Xia, Fangming, 822 Su, P., 756 Thornburg, Kelly R., 177 Suga, Tetsuya, 889 Vickers, S., 631 Thummel, Kenneth E., 947 Sugiyama, Katsumi, 584 Vickers, Stanley, 139 Yabuki, Masashi, 294 Thurman, Ronald G., 680 Sugiyama, Yuichi, 50 Vincent, S. H., 811 Yamaguchi, Toshiro, 616 Tich, Nancy R., 788 Sukbuntherng, Juthamas, 406 Vitarius, James A., 472 Yamamoto, Kenji, 815 Toja, E., 259 Sullivan, James P., 788 Vyas, K. P., 631 Yamaoka, Kiyoshi, 479 Tombret, Francis, 544 Sultatos, Lester 0., 472 Yang, Chung S., 566 Torres-Molina, Francisca, 447 Surber, Bruce W., 788 Wainer, Irving W., 165 Yang, Hsueh-Ying L., 331 Town,C., 211 Suttle, A. Benjamin, 224 Walle, Thomas, 177 Yeh, S. D. J., 643 Trager, William F., 975 Sutton, Steven C., 438 Walz, Jr., Frederick G., 607 Yoshida, Kaoru, 750 Triolo, A., 259 Suzuki, Hiroshi, 50 Wang, Eijia, 566 Yoshida, Motofumi, 312 Trnovec, 1., 338 Svensson, Craig K.. 572 Wang, Li, 8, 561 Yoshida, Toshiaki, 275 Szuna, A., 211 Tsai, Tung-Hu, 518 Wang, Taigi, 165 Yoshitake, Akira, 294 Tse, Francis L. S., 873 Watkins, ifi, John B., 537 Yuan, A. S., 631 Tagaya, Osamu, 561 Tulliez, J., 578 Watkins, Paul B., 947 Yuan, Jinhua, 14 Tajima, Kazuo, 815 Tynes, R., 269 Waxman, David J., 673 Takahara, Eiji, 761 Tzimas, Georg, 928 Wheeler, S. M., 124, 189 Zbaida, Shmuel, 412 Takayama, Yu-ichi, 8 Wichmann, Joseph K., 168 Zenser, Terry V., 922 Tam, Shui-Pang, 248 Uchic, John 1., 880 Wienkers, Larry C., 975 Zhang, Kanyin, 544, 554 Tam, Y. K., 36, 530 Uchino, Katuyoshi, 2 Williams, D. E., 383, 392 Thong, Thi, 680 Tang, Cuyue, 544, 554 Urban, Gudrun, 511 Williams, P. L., 459 Ziemniak, John A., 216 SUBJECT INDEX

A-74273, in vivo and in vitro morpholine ring metabolism (rats, dogs, Antimalarial drug, candidate, WR24251 1, pharmacokinetics and kinetic- humans), 880 dynamic modeling, 358 ABT-41 8, in vitro hepatic metabolism (rats, dogs, cynomolgus monkeys, Antiprotozoal drugs, pentamidine, N-hydroxylation, catalyzed by liver humans), 788 cytochrome P450 2C3 (rabbits), 486 Acetaminophen Antiviral agents, deoxyguanine analogs, as prodrugs, effectiveness and metabolism, cytochrome-P450-dependent, effects of flavonoids, liver enzymology, assessment using in vitro systems (rats, humans), microsomes (rats, humans), 566 124, 189 sulfation, deficient dietary intake of sulfur (rats), 725 ‘25I-Ardeparin, distribution and excretion (rats, dogs), 175 Acetohexamide, carbonyl reductase activity, erythrocytes (humans), 367 Arginine, biological oxidation to /V’3-hydroxyargine, citrullin, and nitric Acetone, acute and chronic administration, induction and regulation of oxide, and N-hydroxylation of pentamidine by P450 2C3, 486 CYP2E1 in murine liver (mice), 248 Avidin, conjugate of, and monoclonal antibody to transferrin receptor, 2-Acetylaminofluorene, cytochrome-P450-dependent biotransformation, biotin bound to, pharmacokinetics and saturable blood-brain bar- cell-free preparations of embryonic tissues (humans), 331 rier transport, 99 N-Acetylbenzidine, glucuronidation, liver (humans), 922 Azo dye substrates, reactivity, determined by electron densities and redox N-Acetyltransferase alleles, polymorphic, mutant and wild-type, cloning, potentials, 412 expression, and functional characterization (humans), 371 Acitretin disposition, oral administration (humans), 211 Baculovirus, cDNA-directed expression of human cytochrome P450 3A4, tissue distribution and elimination, kinetics (rats), 26 688 Acyclovir, prodrugs, valaciclovir Benzo(a)pyrene, storage and metabolism in liver, role of Kupffer cells, metabolic disposition (rats), 60 680 metabolic fate and pharmacokinetics (monkeys), 55 Benzodiazepine, receptor agonist Adenosine, role in renal failure induced by bacterial lipopolysaccharide comparison with GABAA receptor agonist, 50 (rats), 8 partial (L-663,581), physiological disposition (laboratory animals), 693 Adrenal gland, embryonic tissues, cell-free preparations, cytochrome- 3-[2-(Benzoxol-2-yl)ethylJ-5-ethyl-6-methylpyridin-2(1H)-one, see L- P450-dependent biotransformation of 2-acetylaminofluorene (hu- 696,229 mans), 331 Bile Aflatoxin B, disposition of 20(S)-camptothecin, lactone and carboxylate forms (rats), -DNA adducts, hepatic, reduced levels in vivo, association with liver 438 glutathione transferase subunit (Yc2) induction by indole-3-carbi- excretion of taxol, effect of cimetidine, probenecid, and ketoconazole nol (rats), 392 (rats), 254 metabolism, and cytochromes P450 associated with bioactivation and flow, influence on ranitidine pharmacokinetics (rats), 224 detoxication, indole-3-carbinol and 13-naphthoflavone induction Biotin, bound to conjugate of avidin and monoclonal antibody to trans- (rats), 383 femn receptor, pharmacokinetics and saturable blood-brain barrier Alendronate, nonlinear kinetics, plasma protein binding and bone uptake, transport, 99 400 Blood-brain barrier, saturable, transport of biotin bound to conjugate of O6-Alkylguanine-DNA alkyltransferase inhibitor, disposition and metab- avidin and monoclonal antibody to transferrin receptor, 99 olism, nude mice bearing human melanoma, 637 Bone, uptake of alendronate, 400 Allylbenzene, 2,3-epoxide metabolites, detoxication, conjugation with Brain glutathione, 731 blood-brain barrier, saturable, transport of biotin bound to conjugate of Amidoximes, and N-hydroxylation of pentamidine by liver cytochrome avidin and monoclonal antibody to transfemn receptor, 99 P450 2C3 (rabbits), 486 milacemide metabolism, solid-state NMR (rats), 298 Amifostine, and ethyol, metabolic pathways (BALB/c mouse), 895 muscimol, GABAA receptor occupancy, and glucose metabolic re- 8-Aminoquinoline, WR24251 1, pharmacokinetics and kinetic-dynamic sponse, linear relationship (mice), 50 modeling, 358 remacemide hydrochloride, uptake and transformation, 443 Amitriptyline, tissue distribution and metabolism, repeated administration tissue samples, drug concentrations, epileptic patients treated with fel- (rats), 21 bamate (humans), 168 Amphetamine, racemic, disposition kinetics of d- and !-amphetamine, 2-Bromo-(diglutathion-S-yl)hydroquinone, metabolism and toxicity, in intravenous administration (rats), 406 situ perfused kidney (rats), 503 Angiotensin-converting enzyme inhibitors, RU44507, active form, phar- 2-Bromo-3-(diglutathion-S-yl)hydroquinone, metabolism and toxicity, in macokinetics, 601 situ perfused kidney (rats), 503 Angiotensin II receptor antagonists, L-l58,809, disposition (rats, rhesus Buprenorphine, enterohepatic circulation, pharmacokinetic analysis (rats), monkeys), 183 2 Antibiotics, macrolide, in vitro inhibition of terfenadine metabolism, liver Butadiene monoxide (humans), 849 solvolysis (letter), 820 Anticonvulsants, remacemide hydrochloride, brain uptake and biotrans- solvolytic formation of l,2-dichloro-3,4-epoxybutane, physiological formation, 443 conditions, 206 Anticyanide drug, candidate, WR24251 I, pharmacokinetics and kinetic- L-Buthionine SR-sulfoximine, stereoselective pharmacokinetics, patients dynamic modeling, 358 with cancer, 835 Antidepressant drugs, nefazodone, characterization of metabolites, urine 6-tert-Butyl-2,3-epoxy-l,4-benzoquinone, carbonyl reduction by liver ml- and plasma (humans), 304 crosomes and cytosol (rats), 815 Antifungals, azole, in vitro inhibition of terfenadine metabolism, liver 3-tert-Butyl-4-hydroxyanisole, metabolite, carbonyl reduction by liver (humans), 849 microsomes and cytosol (rats), 815 983 984 SUBJECT INDEX

20(S)-Camptothecin, lactone and carboxylate forms, urinary and biliary 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced, hepatocytes as major lo- disposition (rats), 438 cus, embryo liver (chicks), 962 Carbonic anhydrase inhibitors, see Dorzolamide Cytochrome P450 1A2 Carbonyl probes, theophylline N-demethylations, 827 reductase activity, acetohexamide, erythrocytes (humans), 367 role as N-desisopropylase, propranolol metabolism, liver microsomes reduction, 6-tert-butyl-2,3-epoxy-l,4-benzoquinone, by liver micro- (humans), 909 somes and cytosol (rats), 815 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced, hepatocytes as major lo- Carboxylesterases, hepatic microsomal, induction caused by dietary cx- cus, embryo liver (chicks), 962 posure to di(2-ethylhexyl)phthalate, species differences, 889 Cytochrome P450 2B

R( + )- and S( - )-Carvedilol, oxidation by liver microsomes, evidence for induction following dietary administration of linopirdine (mice), 65 stereoselective oxidation and characterization of cytochrome P450 involvement in methoxychlor metabolism (rats, humans), 937 isozymes (rats), 700 Cytochrome P450 2B1, purified liver, inactivation by N-methylcarbazole CCNU, see l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (rats), 343 cDNA, -directed expression of human cytochrome P450 3A4, using Cytochrome P450 284, purified liver, inactivation by N-methylcarbazole baculovirus, 688 (rabbits), 343 Cytochrome P450 2C3, liver, N-hydroxylation of pentamidine (rabbits), Cefadroxil, renal excretion mechanisms, studies, 447 Chloramphenicol, evidence for new metabolic pathways (ducks), 578 486 Cytochrome P450 2C6, mediation of biotransformation of dapsone and l-(2-Chloroethyl)-3-cyclohexyl-l-nitrosourea, suppression of cytochrome monoacetyldapsone to hydroxylamine metabolites, liver micro- P450 2Cl 1 messenger RNA levels, modulation of liver microso- somes (rats), 572 mal cyclophosphamide and ifosphamide activation (rats), 673 Cytochrome P450 2C9, relationship between levels and prototypic cats- p-Chloronitrobenzene, pharmacokinetic study (rats), 275 lytic activities, liver microsomes (humans), 975 m-Chlorophenylpiperazine, major urinary metabolite, isolation and iden- Cytochrome P450 2Cl 1 tification(rats),171 mediation of biotransformation of dapsone and monoacetyldapsone to Cholinergic channel activators, ABT-41 8, in vitro hepatic metabolism hydroxylamine metabolites, liver microsomes (rats), 572 (rats, dogs, cynomolgus monkeys, humans), 788 messenger RNA levels, suppression by l-(2-chloroethyl)-3-cyclohexyl- Chromium, urinary excretion following ingestion of chromium picolinate l-nitrosourea, 673 (humans), 522 oxidation of R(+)- and S(-)-carvedilol, liver microsomes (rats), 700 Cimetidine purified, formation of l6a-hydroxyandrostenedione from testosterone (rats), 254 effect on taxol metabolism (rats), 584 interaction with oxidized and prereduced microsomal cytochrome P450, Cytochrome P450 2Dl, oxidation of R(+)- and S(-)-carvedilol, liver 180 microsomes (rats), 700 renal tubular transport, isolated perfused kidney (rat), 148 Cytochrome P450 2D6 Cisplatin, analog bearing a 1,2-diphenylethylenediamine ligand, revers- involvement in metabolism of 5-hydroxytryptamine antagonists, 269 ible and irreversible interactions with plasma and plasma proteins microsomal preparation, metabolism of methoxyphenamine in vitro, in vitro, 419 756 Citrulline, biological oxidation of arginine, 486 role as nng-hydroxylase, propranolol metabolism, liver microsomes Cocaine, pharmacokinetics, ethanol pretreatment (rats), 498 (humans), 909 Codeine, toxicokinetics, two-year dosed feed study (rats), 14 Cytochrome P450 2El Cyclophosphamide induction and regulation in murine liver, acute and chronic acetone activation, liver microsomes, modulation by l-(2-chloroethyl)-3-cyclo- administration (mice), 248 hexyl-l-nitrosourea (rats), 673 metabolism of 1,1,2,3,3,3-hexafluoropropyl methyl ether, 667 metabolism by lipoxygenases, 74 Cytochrome P450 3A Cyclosporine derivative, SDZ 1MM 125, absorption and disposition, sin- induction following dietary administration of linopirdine (mice), 65 gle and repeated administration (rats), 194 murine, induction by usnic and vulpinic acids, 663 Cyclosporin G, pharmacokinetics and metabolism (humans), 873 role in in vitro metabolism of zatosetron, 352 Cytochrome P450 Cytochrome P450 3Al, mediation of biotransformation of dapsone and associated with bioactivation and detoxification of a.flatoxin B , , influ- monoacetyldapsone to hydroxylamine metabolites, liver micro- ence of indole-3-carbinol and -naphthoflavone (rats), 383 somes (rats), 572 -dependent acetaminophen metabolism, effects of flavonoids, liver mi- Cytochrome P450 3A4 crosomes (rats, humans), 566 cDNA-directed expression using baculovirus (humans), 688 -dependent biotransformation, 2-acetylaminofluorene, cell-free prepa- expression in small bowel, interpatient heterogeneity, lack of prediction rations of embryonic tissues (humans), 331 by erythromycin breath test, 947 genetic and developmental diversity, warfarin and progesterone metab- involvement in FK 506 metabolism, liver microsomes (humans), 811 olism, hepatic microsomes, inbred strains (rats), 607 Cytochrome P450 3A5, expression in small bowel, interpatient heteroge- isozymes, involvement in FK 506 metabolism, liver microsomes (hu- neity, lack of prediction by erythromycin breath test, 947 mans), 811 Cytosol, liver, carbonyl reduction of 6-tert-butyl-2,3-epoxy-l,4-benzoqui- isozymes, involvement in oxidation of R( m+)- and S( )-carvedilol, none (rats), 815 liver microsomes (rats), 700 isozymes, involvement in propranolol metabolism, liver microsomes, Dapsone role of CYP2D6 and CYP1A2 (humans), 909 amino acid prodrugs, pharmacokinetics, 770 microsomal, oxidized and prereduced, interaction of cimetidine with, biotransformation to hydroxylamine metabolites, mediation by cyto- 180 chrome P450 2C6/2Cll and 3A1, liver microsomes (rats), 572 Cytochrome P450 1A1 N-hydroxylation, monoacetyldapsone inhibition, liver microsomes (hu- probes, theophylline N-demethylations, 827 mans, rats), 161 SUBJECT INDEX 985

pharmacokinetics, 770 cotreatment, suppression of in vivo clearance of N-nitrosodimethyl- DEET, dermal absorption, pharmacokinetic assessment (cattle), 106 amine (mice), 43 N-Deethylated dorzolamide, in vitro binding to erythrocytes (humans), pretreatment, cocaine pharmacokinetics (rats), 498 377 Ethyol, and amifostine, metabolic pathways (BALB/c mouse), 895 Deoxyguanine analogs, as prodrugs of antiviral agents, effectiveness and Etretinate, tissue distribution and elimination, kinetics (rats), 31 enzymology, assessment using in vitro systems (rats, humans), Exercise, chronic voluntary, effect on hepatobiliary clearance of chemi- 124, 189 cals (rats), 537 Dichloroacetylene, glutathione and cysteine S-conjugates, glutathione- dependent biosynthesis and bloactivation, tissues and subcellular Famotidine, renal excretion, renal failure induced by bacterial lipopoly- fractions (rats), 143 saccharide (rats), 8 I ,2-Dichloro-3,4-epoxybutane, solvolytic formation from butadiene mon- Felbamate, drug concentrations, brain tissue samples, epileptic patients oxide, physiological conditions, 206 (humans), 168 2,2-Dichloro- I , I , 1-trifluoroethane (HCFC- I 23), gas-uptake pharmacoki- Fibrinogen receptor antagonists, MK-852, disposition (rats, dogs), 631 netics, 5 1 1 Finasteride, biotransformation, in vitro, hepatic microsomes, isolation and S-(l,2-Dichlorovinyl)glutathione, glutathione-dependent biosynthesis and characterization of metabolites (rats), 79 bioactivation, tissues and subcellular fractions (rats), 143 FK 506 s- I,2-Dichlorovinyl-L-cysteine, glutathione-dependent biosynthesis and metabolism, liver microsomes, involvement of cytochrome P450 bioactivation, tissues and subcellular fractions (rats), 143 isozymes, investigation (humans), 8 1 1 Diclofenac metabolism, male and female liver microsomes (rats), 85 covalent adduct formation to hepatic microsomal proteins, mechanism Flavonoids, effects on cytochrome-P450-dependent acetaminophen me- (rats), 956 tabolism, liver microsomes (rats, humans), 566 enterohepatic circulation, disposition kinetics, new analysis method 5-[’8F]Fluoro-2-deoxyuridine, hepatic arterially injected, transport limits (rats), 479 cellular entry, intrahepatic tumors (humans), 643 Diethyldithiocarbamate methyl ester, NADPH-dependent, regioselective S-oxidation, liver microsomes (rats), 324 Glucagon, effects on propranolol disposition, single-pass isolated, per- N,N-Diethyl-m-toluamide, see DEET fused liver (rats), 822 l,3-Di(4-imidazolino-2-methoxyphenoxy)propanelactate, pharmacoki- Glucose, metabolic response, and GABAA receptor occupancy of musci- netics (dogs), 233 mol, linear relationship, conscious brain (mice), 50 Diltiazem Glucuronic acid, moiety, retention in diclofenac-protein adducts, hepatic effects on disposition and metabolism of enantiomers of propranolol, microsomes (rats), 956 multiple oral dosing (dog), 776 N-Glucuronidation reactions, methylbiphenyl tetrazole, methylbiphenyl kinetic interactions with lidocaine, diphenhydramine, and verapamil, triazole, and methylbiphenyl imidazole isolated perfused liver (rats), 530 regioselectivity of N-glucuronidation, recombinant UDP-glucuronosyl- time-dependent kinetics, mechanisms, isolated perfused liver (rats), 36 transferases stably expressed in V79 cells (humans, rats), 659 Diphenhydramine, kinetic interaction with diltiazem, isolated perfused relative N-glucuronidation reactivity, hepatic microsomes (rats, mon- liver (rats), 530 keys, humans), 651 Di(2-ethylhexyl)phthalate, dietary exposure, induction of hepatic micro- Glutamate antagonist, neuroprotective, see NBQX somal carboxylesterases, species differences, 889 Glutathione DMP 323, pharmacokinetics (rats, dogs), 709 conjugation with, detoxication of 2,3-epoxide metabolites of allylben- DNA adducts, aflatoxin-, hepatic, reduced levels in vivo, association with zene and estragole, 731 liver glutathione transferase subunit (Yc2) induction by indole-3- -dependent biosynthesis and bioactivation, glutathione and cysteine carbinol (rats), 392 S-conjugates of dichloroacetylene, tissues and subcellular fractions 1,2-Diphenylethylenediamine ligand, cisplatin analog bearing, reversible (rats), 143 and irreversible interactions with plasma and plasma proteins in intraperitoneal administration with tetraplatin, pharmacokinetics (mice), vitro, 419 312 Dolastatin 10, preclinical pharmacology, 428 S-transferases, cytosolic, increased cosedimentation with microsomal Dopamine D-l receptor antagonists fractions prepared from frozen liver (rats), 964 SCH 23390, glucuronidation by liver microsomes (humans), 713 transferase subunit (Yc2), liver, induction by indole-3-carbinol (rats), SCH 39166, glucuronidation by liver microsomes (humans), 713 392 Dorzolamide Growth hormone-releasing peptide (SK&F 1 10679), disposition, intrave- and metabolite, N-deethylated dorzolamide, in vitro binding to eryth- nous or subcutaneous administration (rats, dogs), 90 rocytes (humans), 377 in vitro metabolism, liver microsomes (rats), 916 Heart, embryonic tissues, cell-free preparations, cytochrome-P450-depen- Enprofylline, pharmacokinetics and protein binding, alterations, hyperbi- dent biotransformation of 2-acetylaminofluorene (humans), 331 lirubinemia, rats, 561 Hematopoiesis, negative regulators, seraspenide, pharmacokinetics, 843 Erythrocytes Heparin, ‘25I-ardeparin, distribution and excretion (rats, dogs), 175 binding of dorzolamide and N-deethylated dorzolamide, in vitro (hu- Hepatocytes mans), 377 locus of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYPI-related carbonyl reductase activity for acetohexamide (humans), 367 P450s, TCDDAA and TCDDAHH, embryo liver (chicks), 962 Eryth.romycin breath test, lack of prediction of interpatient heterogeneity, thapsigargin metabolism (rats), 433 expression of CYP3A4 and CYP3A5 in small bowel, 947 1,1,2,3,3,3-Hexafluoropropyl methyl ether, metabolism, role of cyto- Estragole, 2,3-epoxide metabolites, detoxication, conjugation with gluts- chrome P450 2E1 , 667 thione, 731 Human immunodeficiency virus- 1 Ethanol protease inhibitors, DMP 323, pharmacokinetics (rats, dogs), 709 986 SUBJECT INDEX

reverse transcriptase inhibitors, i-696,229, metabolism (rats, humans), Lipopolysaccharide-induced renal failure, excretion of famotidine and 200, 281 role of adenosine (rats), 8 16a-Hydroxyandrostenedione, formation from testosterone, purified P450 Lipoxygenases, metabolism of cyclophosphamide, 74 2Cl 1 (rats), 584 Liver N#{176}-Hydroxyarginine, biological oxidation of arginine, 486 N-acetylbenzidine, glucuromdation (humans), 922 Hydroxylamine metabolites, biotransformation of dapsone and mono- benzo(a)pyrene, storage and metabolism, role of Kupifer cells, 680 acetyldapsone, mediation by cytochrome P450 2C6/2C1 1 and 3A1, cytochrome P450 2C3, N-hydroxylation of pentamidine (rabbits), 486 liver microsomes (rats), 572 diltiazem, time-dependent kinetics, mechanisms (rats), 36 6a-Hydroxytaxol, isolation and identification, liver microsomes (hu- embryo, tetrachlorodibenzo-p-dioxin-induced CYP1-related P450s, TC- mans), 177 DDAA, and TCDDAHH, hepatocytes as major locus (chicks), 962 3-Hydroxy-thiomethyl metabolites, production, hepatic metabolism of embryonic tissues, cell-free preparations, cytochrome-P450-dependent spironolactone, 903 biotransformation of 2-acetylaminofluorene (humans), 331 5-Hydroxytryptamine antagonists enterohepatic circulation ondansetron, metabolism, CYP2D6 involvement, 269 buprenorphine, pharmacokinetic analysis (rats), 2 tropisetron, metabolism, CYP2D6 involvement, 269 diclofenac, disposition kinetics, new analysis method (rats), 479 Hyperbilirubinemia, enprofylline, alterations in pharmacokinetics and norbuprenorphine, pharmacokinetic analysis (rats), 2 protein binding, rats, 561 recirculation, pharmacokinetics of ranitidine (rats), 224 Hypoglycemic agents, pioglitazone, disposition and metabolism (rats), enterohepatic cycling, N#{176}-nitro-L-arginine (rats), 338 625 hepatobiliary clearance, endogenous and exogenous chemicals, effect of chronic voluntary exercise (rats), 537 Ifosfamide induction and regulation of CYP2E1, acute and chronic acetone admin- activation, liver microsomes, modulation by l-(2-chloroethyl)-3-cyclo- istration (mice), 248 hexyl-l-nitrosourea (rats), 673 intrahepatic tumors, hepatic arterially injected 5-[’8F]fluoro-2-deoxy- enantiomers, enantioselective N-dechloroethylation, influence of phe- uridine, transport limits cellular entry (humans), 643 nobarbital induction (rats), 165 kinetic interactions of lidocaine, diphenhydramine, and verapamil with Immunosuppressants FK 506, metabolism, liver microsomes, involvement of cytochrome diltiazem (rats), 530 P450 isozymes, investigation (humans), 81 1 metabolism of ABT-418, in vitro (rats, dogs, cynomolgus monkeys, FK 506, metabolism, male and female liver microsomes (rats), 85 humans), 288 Indole-3-carbinol metabolism of L-696,229 (rats, humans), 200, 281 induction of aflatoxin B, metabolism and cytochromes P450 associated metabolism of spironolactone, production of 3-hydroxy-thiomethyl me- with aflatoxin B, bioactivation and detoxification (rats), 383 tabolites, 903 induction of liver glutathione transferase subunit with high activity milacemide metabolism, solid-state NMR (rats), 298 toward aflatoxin B, exo-epoxide (rats), 392 propranolol disposition, presence and absence of insulin and glucagon Insulin, effects on propranolol disposition, single-pass isolated, perfused (rats), 822 liver (rats), 822 purified cytochmme P450, inactivation by N-methylcarbazole (rats, Intestine, site-dependent hydrolysis, vaiproate and morphine glucuronide rabbits), 343 (rats), 120 UDP-glucuronosyltransferase, stable expression, with activity toward Isbufylline, metabolism (humans), 259 steroid and xenobiotic substrates (humans), 799 Liver microsomes Ketoconazole, effect on taxol metabolism (rats), 254 azoreductase activity, 412 Kidney carbonyl reduction of 6-tert-butyl-2,3-epoxy-l,4-benzoquinone (rats), cefadroxil, excretion mechanisms, 447 815 cimetidine, renal tubular transport (rats), 148 carboxylesterases, induction, caused by dietary exposure to di(2-ethyl- embryonic tissues, cell-free preparations, cytochrome-P450-dependent hexyl)phthalate, species differences, 889 biotransformation of 2-acetylaminofluorene (humans), 331 R(+)- and S(- )-carvedilol oxidation, evidence for stereoselective oxi- failure, bacterial lipopolysaccharide-induced, renal excretion of famo- dation and characterization of cytochrome P450 isozymes (rats), tidine and role of adenosine (rats), 8 700 inorganic sulfate, transport, inhibition by salicylate, membrane vesicle cyclophosphamide and ifosphamide activation, modulation by 1-(2- preparations (rats), 318 chloroethyl)-3-cyclohexyl-l-nitrosourea (rats), 673 metabolism and toxicity of 2-bromo-(diglutathion-S-yl)hydroquinone cytochrome P450-dependent acetaminophen metabolism, effects of fla- and 2-bromo-3-(diglutathion-S-yl)hydroquinone (rats), 503 vonoids (rats, humans), 566 Kupffer cells, role in storage and metabolism of benzo(a)pyrene, liver, levels and prototypic catalytic activities, relationship (humans), 975 680 dapsone and monoacetyldapsone, biotransformation to hydroxylamine metabolites, mediation by cytochrome P450 2C6/2C1 I and 3A1 L-l58,809, disposition (rats, rhesus monkeys), 183 (rats), 572 L-663,58l, physiological disposition (laboratory animals), 693 dapsone N-hydroxylation, monoacetyldapsone inhibition (humans, L-696,229, metabolism (rats, humans), 200, 281 rats), 161 (R),(R)-Labetalol, urinary metabolites, 866 diethyldithiocarbamate methyl ester, regioselective S-oxidation (rats), Lichen constituents, usnic and vulpinic acids, induction of murine cyto- 324 chrome P450 3A, 663 dopamine D-l receptor antagonists, glucuronidation (humans), 713 Lidocaine, kinetic interaction with diltiazem, isolated perfused liver (rats), dorzolamide, in vitro metabolism (rats), 916 530 finasteride biotransformation, isolation and characterization of metab- Linopirdine, dietary administration, induction of cytochromes P450 2B olites (rats), 79 and 3A (mice), 65 FK 506 metabolism (rats), 85 SUBJECT INDEX 987

FK 506 metabolism, involvement of cytochrome P450 isozymes, in- NBQX (6-nitro-7-sulfamoyl-benzo(f)-quinoxaline-2,3-dione), pharmaco- vestigation (humans), 811 kinetics (mice, rats, dogs), 289 N-glucuronidation reactivity, relative, methylbiphenyl tetrazole, meth- Nefazodone, characterization of metabolites, urine and plasma (humans), ylbiphenyl triazole, and methylbiphenyl imidazole (rats, monkeys, 304 humans), 651 Nithc oxide, biological oxidation of arginine, 486 N-hydroxylation of pentamidine (humans), 486 N#{176}-Nitro-L-arginine, enterohepatic cycling (rats), 338 6a-hydroxytaxol, isolation and identification (humans), 177 N-Nitrosodimethylamine, in vivo clearance, suppression by cotreatment p-nitrophenol hydroxylase, inhibition by small aromatic and heterocy- with ethanol (mice), 43 clic molecules (rats), 806 p-Nitrophenol hydroxylase, in liver microsomes, inhibition by small aro- proteins, covalent adduct formation of diclofenac, mechanism (rats), matic and heterocyclic molecules (rats), 806 956 Norbuprenorphine, enterohepatic circulation, pharmacokinetic analysis pseudoracemic propranolol, metabolic kinetics (humans), 237 (rats), 2 warfarin and progesterone metabolism, inbred strains (rats), 607 NSC 376128, see Dolastatin 10 Lomustine, see l-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea Nuclear magnetic resonance, solid-state, milacemide metabolism, liver Lung, embryonic tissues, cell-free preparations, cytochrome-P450-depen- and brain slices (rats), 298 dent biotransformation of 2-acetylaminofluorene (humans), 331

Ondansetron, metabolism, CYP2D6 involvement, 269 Magnolol, disposition, intravenous bolus and infusion (rabbits), 518 Organophosphates [3H1-I-Menthol, metabolic fate (rats), 616 paraoxon, detoxification by serum A-esterase, kinetic mechanism (hu- Methoxychlor, metabolism by hepatic P450 monooxygenases, dual path- mans), 472 ways involving novel ortho ring-hydroxylation by CYP2B (rats, parathion, percutaneous absorption, biotransformation and systemic humans), 937 absorption, in vivo (swine), 459 Methoxyphenamine, metabolism in vitro by CYP2D6 microsomal prepa- ration, 756 Paraoxon, detoxification by serum A-esterase, kinetic mechanism (hu- Methylbiphenyl imidazole mans), 472 N-glucuronidation reactivity, hepatic microsomes (rats, monkeys, hu- Parathion, percutaneous absorption, biotransformation and systemic ab- mans), 651 sorption, in vivo (swine), 459 regioselectivity of N-glucuronidation, recombinant UDP-glucuronosyl- Pentamidine, N-hydroxylation, catalyzed by liver cytochrome P450 2C3 transferases stably expressed in V79 cells (humans, rats), 659 (rabbits), 486 Methylbiphenyl tetrazole Peroxisome proliferators, di(2-ethylhexyl)phthalate, dietary exposure, in- N-glucuronidation reactivity, hepatic microsomes (rats, monkeys, hu- duction of hepatic microsomal carboxylesterases, species differ- mans), 651 ences, 889 regioselectivity of N-glucuronidation, recombinant UDP-glucuronosyl- Phenobarbital, induction, influence on enantioselective N-dechloroethyla- transferases stably expressed in V79 cells (humans, rats), 659 tion of ifosfamide enantiomers (rats), 165 Methylbiphenyl triazole 3-Phosphoadenosine 5-phosphosulfate, homeostasis, acetaminophen- N-glucuronidation reactivity, hepatic microsomes (rats, monkeys, hu- induced alterations, deficient dietary intake of sulfur (rats), 725 mans), 651 Pioglitazone, disposition and metabolism (rats), 625 regioselectivity of N-glucuronidation, recombinant UDP-glucuronosyl- Plasma transferases stably expressed in V79 cells (humans, rats), 659 all-trans- and 9-cis-retinoic acid, oral administration, differences in N-Methylcarbazole, inactivation of cytochrome P450 (rats, rabbits), 343 pharmacokinetic properties (mice), 451 L-a-Methyldopa, metabolism, in vivo, comparison with metabolism in and plasma proteins, in vitro, reversible and irreversible interactions of cultured intestinal epithelial cell monolayers (humans), 592 a cisplatin analog with, 419 4-[4-(4-Methylphenyl)-phenylmethoxy-1 -piperidinyljbutyric acid, dispo- metabolites of isbufylline, isolation, identification, and synthesis (hu- sition, inter-individual differences, possible involvement of genetic mans), 259 polymorphism (rats), 761 metabolites of nefazodone, characterization (humans), 304 Milacemide, metabolism in liver and brain slices, solid-state NMR (rats), metabolites of 9-cis-retinoic acid, 928 298 protein binding, alendronate, 400 MK-852, disposition (rats, dogs), 631 Primaquine, analog WR24251 I, pharmacokinetics and kinetic-dynamic Mofegiline, novel carbamate metabolites (dogs, humans), 738 modeling, 358 Monoacetyldapsone, biotransformation to hydroxylamine metabolites, Probenecid mediation by cytochrome P450 2C6/2Cl I and 3A1, liver micro- effect on total metabolism (rats), 254 somes (rats), 572 interactions with NBQX (mice, rats, dogs), 289 Monoamine oxidase B, inhibitors, Mofegiline, novel carbamate metabo- Proestrogenic pesticides, methoxychlor, metabolism by hepatic P450 mo- lites (dogs, humans), 738 nooxygenases, dual pathways involving novel ortho ring-hydroxy- Morphine glucuronide, site-dependent intestinal hydrolysis (rats), 120 lation by CYP2B (rats, humans), 937 Muscimol, GABAA receptor occupancy, and glucose metabolic response, Progesterone, metabolism by hepatic microsomes, inbred strains (rats), linear relationship, conscious brain (mice), 50 607 Propranolol NAc-SDKP, see Seraspenide disposition, single-pass isolated, perfused liver, presence and absence of NADPH-dependent, regiosclective S-oxidation, diethyldithiocarbamate insulin and glucagon (rats), 822 methyl ester, liver microsomes (rats), 324 enantiomers, disposition and metabolism, effects of diltiazem, multiple

-Naphthoflavone, induction of aflatoxin , metabolism and cytochromes oral dosing (dog), 776

P450 associated with aflatoxin B , bioactivation and detoxification metabolism, involvement of cytochrome P450 isozymes, liver micro- (rats), 383 somes, role of CYP2D6 and CYPIA2 (humans), 909 988 SUBJECT INDEX

pseudoracemic, metabolic kinetics, liver microsomes (humans), 237 inorganic, renal transport, inhibition by salicylate, membrane vesicle Pseudoracemic propranolol, metabolic kinetics, human liver microsomes, preparations (mice), 318 237 Tacrine, stereoselective hydroxylation (rats, humans), 719 Quinidine inhibition, pseudoracemic propranolol, metabolic kinetics, liver Taxol microsomes (humans), 237 distribution, biliary secretion, and metabolism, effect of cimetidine, Ranitidine, pharmacokinetics, influence of bile flow (rats), 224 probenecid, and ketoconazole (rats), 254 Remacemide-glycine hydrolase, tissue distribution and stereoselectivity, 6a-hydroxytaxol, isolation and identification, liver microsomes (hu- 973 mans), 177 Remacemide hydrochloride, brain uptake and biotransformation, 443 Terfenadine, metabolism, liver, in vitro inhibition by macrolide antibiotics Renin inhibitors, orally active, A-74273, in vivo and in vitro morpholine and azole antifungals (humans), 849 ring metabolism (rats, dogs, humans), 880 Testosterone, formation of 16a-hydroxyandrostenedione, purified P450 Retinoic acid 2Cl I (rats), 584 aIl-trans- and 9-cis-, oral administration, differences in pharmacokinetic Tetrachlorodibenzo-p-dioxin, -induced CYPI-related P450s, TCDDJ, properties, plasma (mice), 451 and TCDDAHH, hepatocytes as major locus, embryo liver (chicks), pharmacokinetics, intravenous administration (monkeys), 154 962 all-trans-4-oxo, pharmacokinetics, intravenous administration (mon- Tetraplatin, pharmacokinetics, administered intraperitoneally with re- keys), 154 duced glutathione (mice), 312 9-cis- and all-trans-, oral administration, differences in pharmacokinetic Thapsigargin, metabolism in hepatocytes (rats), 433 properties, plasma (mice), 451 Theophylline, N-demethylations, probes for P45O1AI and P4501A2, 827 limited placental transfer to embryos (mice, rats), 928 Thiabendazole, formation of toxic metabolites, identification of thioam- major plasma metabolites, 9,l3-dicis-retinoic acid, 928 ides as ring cleavage products (mice), 750 9,l3-dicis- identification as major plasma metabolite of 9-cis-retinoic Thiazoles, formation of toxic metabolites, identification of thioamides as acid, 928 ring cleavage products (mice), 750 limited placental transfer to embryos (mice, rats), 928 Thioamides, identification as ring cleavage products, formation of toxic I 3-cis-, pharmacokinetics, intravenous administration (monkeys), 154 metabolites from thiazoles (mice), 750 13-cis-4-oxo, pharmacokinetics, intravenous administration (monkeys), Tissue distribution studies, routine, for approval of human drugs, purpose 154 and cost effectiveness questioned (letter), 341 Retinoid drugs, tissue distribution and elimination, kinetics (rats), 26, 31 Transferrin receptor, monoclonal antibody to, and conjugate of avidin, RG 14620, dispositional characteristics, intravenous administration or biotin bound to, pharmacokinetics and saturable blood-brain bar- dermal application (rats, rabbits), 216 rier, 99 Risperidone, metabolism and excretion, oral administration (rats, dogs), Trichloroethylene, metabolism, quantification, vial equilibration method, 129 comprehensive evaluation, 858 RNA, messenger, suppression of cytochrome P450 2Cl 1 levels, modula- Tropisetron, metabolism, CYP2D6 involvement, 269 tion of liver microsomal cyclophosphamide and ifosphamide acti- Tyrosine kinase inhibitor (RG 14620), dispositional characteristics, intra- vation (rats), 673 RU44403, pharmacokinetics (rats), 601 venous administration or dermal application (rats, rabbits), 216 RU44507, active form, pharmacokinetics (rats), 601 UDP-glucuronosyltransferase, liver, stable expression, with activity to- Salicylate, renal transport of inorganic sulfate inhibition, membrane yes- ward steroid and xenobiotic substrates (humans), 799 ide preparations (mice), 318 Urine SCH 23390, glucuronidation by liver microsomes (humans), 713 disposition of2O(S)-camptothecin, lactone and carboxylate forms (rats), SCH 39166, glucuronidation by liver microsomes (humans), 713 438 SDZ 1MM 125, absorption and disposition, single and repeated adminis- excretion of chromium, following ingestion of chromium picolinate tration (rats), 194 (humans), 522 Seraspenide, pharmacokinetics, healthy volunteers and patients, 843 major metabolite of m-chlorophenylpiperazine, isolation and identifica- Serum, A-esterase, detoxification of paraoxon, kinetic mechanism (hu- tion (rats), 171 mans), 472 metabolites of isbufylline, isolation, identification, and synthesis (hu- Simvastatin, metabolic disposition, patients with T-tube drainage, 139 mans), 259 SK&F 1 10679 (growth hormone-releasing peptide), disposition, intrave- metabolites of (R),(R)-labetalol, 866 nous or subcutaneous administration (rats, dogs), 90 metabolites of nefazodone, characterization (humans), 304 Skin, absorption of DEET, pharmacokinetic assessment (cattle), 106 Usnic acid, induction of murine cytochrome P450 3A, 663 SM-10888, and metabolites, pharmacokinetics depending upon physico- chemical properties, 294 Spironolactone, hepatic metabolism, production of 3-hydroxy-thiomethyl Valaciclovir metabolites, 903 metabolic disposition (rats), 60 Steroids, substrates, liver UDP-glucuronosyltransferase with activity to- metabolic fate and pharmacokinetics (monkeys), 55 ward, stable expression (humans), 799 Valproate, site-dependent intestinal hydrolysis (rats), 120 Stiripentol, metabolic chiral inversion Valproic acid, disposition and protein binding (rats), 113 influence of administration route (rats), 554 Verapamil, kinetic interaction with diltiazem, isolated perfused liver mechanistic studies (rats), 544 (rats), 530 Sulfate Volatile organic chemicals, metabolism, quantification, vial equilibration homeostasis, acetaminophen-induced alterations, deficient dietary in- method, comprehensive evaluation, 858 take of sulfur (rats), 725 Vulpinic acid, induction of murine cytochrome P450 3A, 663 SUBJECTINDEX 989

Warfarin, metabolism by hepatic microsomes, inbred strains (rats), 607 substrates, liver UDP-glucuronosyltransferase with activity toward, sta- WR24251 1, pharmacokinetics and kinetic-dynamic modeling, 358 ble expression (humans), 799 WR-2721 (ethyol, amifostine), metabolic pathways (BALB/c mouse), 895

Xenobiotics Z&inoni, Vincent G., dedication, 1 diethyldithiocarbamate methyl ester, regioselective S-oxidation, liver t0setr0fl, in vitro metabolism, interspecies comparison and role of CYP microsomes (rats), 324 3A, 352 9 4

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Raymond F. Novak, Editor Russell Prough, Gerald Miwa, and Stephen P. Spielberg, Associate Editors Elizabeth Sherman, Assistant to the Editor

Editorial Advisory Board

Ghulam A. S. Ansari Fred F. Kadlubar Andrew Parkinson Arthur Atkinson Laurence S. Kaminsky Cecil B. Pickett Thomas Baillie Ralph E. Kauffman Lance R. PohI John R. Bend Gregory L. Kedderis John J. Reiners, Jr. Terrence F. Blaschke Dennis R. Koop Kenneth W. Renton Kenneth Brouwer Serrine S. Lau Arleen B. Rifkind Alan R. Buckpitt John J. Lech Robert Ronfeld Arthur K. Cho Anthony Y. H. Lu Catherine Fenselau Bettie Sue Masters Dhiren Thakker Joseph Gal Charlene A. McQueen William Trager Frank J. Gonzalez Bruce Mico Steve U nger Frederick Peter Guengench Terrence J. Monks Mary Vore Phillip S. Guzelian Edward T. Morgan Paul A. Watkins James R. Halpert Sidney D. Nelson David J. Waxman Robert Hanzlik Richard T. Okita Richard M. Weinshilboum Michael J. Olson Ronald N. Hines Ronald E. White Paul F. Hollenberg Curtis Omiecinski Steven A. Wrighton Margaret 0. James Garold S. Yost

Board of Publications Trustees

Kenneth E. Moore, Chairman Marlene L. Cohen Raymond F. Novak D. Craig Brater T. Kendall Harden Marcus M. Reidenberg William A. Catterall John A. Harvey Robert E. Stitzel

Executive Officer

Kay A. Croker

VOLUME 22 1994 Copyright © 1994 by The American Society for Pharmacology and Experimental Therapeutics THEJOURNAL OF PHARMACOLOGYAND EXPERIMENTAL THERAPEUTICS

Editor: John Harvey, PhD, The Medical College of Pennsylvania

JPET is respected the world over as one ofthe leading research journals in the field ofpharmacology. Readers find broad coverage ofall aspects ofthe interactions ofchemicals with biological systems, including:

. autonomic pharmacology #{149}drug abuse

. analgesia drug metabolism

. behavioral pharmacology & disposition

. cardiovascular . gastrointestinal pharmacology pharmacology

. cellular pharmacology . immunopharmacology

. chemotherapy . neuropharmacology

. clinical pharmacology . pulmonary pharmacology

. developmental . renal pharmacology pharmacology . toxicology

JPET is valuable reading for academic, industrial arid clinical pharmacologists as well as toxicologists. Thejournal deserves a place in every pharmaceutical and toxicological research laboratory and pharmacology/toxicology department through- out the world.

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