CONTRIBUTORS

Dr. Melvin E. Andersen Chemical Ind. Institute of Toxicology 6 Davis Drive Research Triangle Park, NC 27709

Prof. Luc P. Balant Psychiatric Univ. Institutions of Geneva 47 rue du XXXI Decembre 1207 Geneve Switzerland

Prof. James S. Beck 4959 Vantage Crescent N.W. Calgary, Alberta. T3A lX6 Canada

Dr. A. Bertrand Brill Department of Nuclear Medicine U.Mass. Medical Center Worcester, MA 01655

Dr. Michel Eichelbaum Fischer-Bosch-Institut fur Klinische Pharmakologie Auerbachstrasse 112 7000 Stuttgart 50 Germany

Dr. Julie Eiseman Division of Developmental Therapeutics University of Maryland Cancer Center 655 West Baltimore Street Baltimore, MD 21201

Dr. Alan Fischman Division of Nuclear Medicine Massachusetts General Hospital Boston, MA 02114

Dr. Daniel R. Krewski Room 109 Environmental Health Center Tunney's Pasture Ottawa, Ontario KIA OL2 Canada

Prof. Giuliano Mariani C.N.R. Fisiologia Clinica via Savi 8 . 56100Pisa Italy

Dr. Bemard M. Maziere Service Hospitalier ''Frederic Joliot" 4, Place du General-Leclerc 91406 Orsay France

Dr. Joyce Mordenti Genentech, Inc. 460 Point San Bruno Blvd. South San Francisco, CA 94080

Prof. Aldo Rescigno School of Pharmacy University of Parma Via Massimo d' Azeglio 85 43100 Parma Italy

Prof. Malcolm Rowland Department of Pharmacy University of Manchester Oxford Road Manchester M13 9PL U.K.

425

Dr. David E. Schafer Veterans Administration Medical SelVice West Haven, CT 06516

Dr. James T. Stevens Director of Toxicology Ciba-Geigy Corp. 410 Swing Road Greensboro, NC 27409

Dr. Alberto Tajana Recordati Industria Chimica via M. Civitali 1 20148 Milano Italy

426

Prof. Bernard Testa Ecole de Phannacie Universite de Lausanne place du Chateau 3 1005 Lausanne Switzerland

Dr. Ajit K. Thakur Hazleton Laboratories America 9200 Leesburg Turnpike Vienna, VA 22180

PARTICIPANTS

Gun Almquist Dept. Human Phannacokinetics Explorative Clinical Research AB Draco, Box 34 S-22100 Lund, Sweden

Dr. Melvin E. Andersen Chemical Ind. Institute of Toxicology 6 Davis Drive Research Triangle Park, NC 27709 U.S.A.

Dr. Riccardo Bellina Istituto di Patologia Medica I Universita degli Studi Pisa, Italy

Dr. Walter Bencivelli CNR Fisiologia Clinic a via Savi 8

1-56100 Pisa, Italy

Dr. Marta Benedetti Istituto Superiore di Sanita

Prof. Luc P. Balant Laboratorio di Tossicologia Comparata Psychiatric Univ. Institutions of Geneva viale Regina Elena 299 47 rue du XXXI Decembre 00161 Roma, Italy 1207 Geneve, Switzerland Dr. Giuseppina Benoni Dr. Virgilio Ballabeni Istituto di Fannacologia Istituto di Fannacologia e Fannacognosia Policlinico Borgo Roma Universita di Panna 37134 Verona, Italy via Massimo d' Azeglio 85 43100 Panna, Italy Prof. Nazan Bergisadi

Dept. Phannaceutical Technology Dr. Elisabetta Barocelli Faculty of Phannacy Istituto di Fannacologia e Fannacognosia Univ. Istanbul Universita di Panna Beyazit - Istanbul, Turkey via Massimo d' Azeglio 85 43100 Parma, Italy

Prof. James S. Beck Division of Medical Biophysics University of Calgary

Dr. Donata Bertin Dipart. Farmacocinetica e Metabolismo Farmitalia - Carlo Erba via Imbonati 24 20159 Milano, Italy

Dr. Bianca Maria Bocchialini 2920 - 24th Ave.N.W. Calgary, Canada

Dr. S. Eralp Bellibas Istituto di Fannacologia e Fannacognosia Universita di Panna

Ege Tip Fakultesi Fannakoloji Anabilim Dali Bornova - Izmir, Turkey

via Massimo d' Azeglio 85 43100 Panna, Italy

427

Eva Bondesson Department of Human Pharmacokinetics Explorative Clinical Research AB Draco, Box 34 S-22100 Lund, Sweden

Dr. A. Bertrand Brill Department of Nuclear Medicine U .Mass. Medical Center Worcester, MA 01655, U.S.A.

Dr. Richard C. Brundage Department of Pharmaceutics College of Pharmacy University of Minnesota 308 Harvard Street S.E. Minneapolis, MN 55455, U.S.A

Dr. Paola Brusa Istituto Chimica Farmaceutica Applicata corso Raffaello 31 10125 Torino, Italy

Harry Bushe Department of Nuclear Medicine U. Mass. Medical Center Worcester, MA 01655, U.S.A.

Dr. Begoiia Calvo Departamento de Farmacia A vda. del Campo Charro bIn 37008 Salamanca, Spain

Dr. Giovanni Cosmi Life Science Research Roma Toxicology Centre SpA via Tito Speri 12/14 00040 Pomezia (Roma), Italy

Dr. Marco Criscuoli Laboratori Guidotti S.p.A. via Livornese 402 56010 S. Piero a Grado (PI), Italy

Dr. Jack Dacre U. S. Army Biomedical Research and Development Laboratory Fort Dietrich Frederick, MD 21702, U.S.A.

Dr. Peter Terence Daley-Yates Department of Pharmacy University of Manchester Oxford Road Manchester M13 9PL, U. K.

428

Dr. Michael David BykGulden Postfach 6500 D-7750 Konstanz, Germany

Dr. B. E. Davies SmithKline Beecham Pharmaceuticals Coldharbour Road The Pinnacles Harlow, Essex CM19 5AD, U. K.

Dr. D. Domurado Universite de Technologie de Compiegne Departement Genie Biologique Centre de Recherches de Royallieu Compiegne, France

Dr. Franco Dosio Istituto di Chimica Farmaceutica Applicata corso Raffaello 31 10125 Torino, Italy

Dr. Constantin Efthymiopoulos Dipart. Farmacocinetica e Metabolismo Farmitalia - Carlo Erba via Imbonati 24 20159 Milano, Italy

Dr. Michel Eichelbaum Fischer-Bosch-Institut flir Klinische Pharmakologie Auerbachstrasse 112 7000 Stuttgart 50, Germany

Dr. Julie Eiseman Division of Developmental Therapeutics University of Maryland Cancer Center 655 West Baltimore Street Baltimore, MD 21201, U.S.A.

Dr. William F. Elmquis Department of Pharmaceutics College of Pharmacy University of Minnesota 308 Harvard Street S.E. Minneapolis, MN 55455, U.S.A.

Prof. Laszlo Endrenyi Department of Pharmacology Medical Sciences Building University of Toronto Toronto, Ontario M5S 1A8, Canada

Prof. Jorge Errecalde Catedra de Farmacologia Facultad de Ciencias Veterinarias Universidad Nacional de La Plata CC 296.1900 La Plata, Argentina

Dr. Luigi Ferran~e .. Facolta di Medicma e Chrrurgm Universita degli Studi di Ancona Ancona, Italy

Dr. Franca Ferrari Dipartimento di Chimica Fannaceutica Universitll. di Pavia viale Taramelli 12 27100 Pavia, Italy

Dr. Alan Fischman Division of Nuclear Medicine Massachusetts General Hospital Boston, MA 02114, U.S.A.

Dr. Roberto Foroni Servizio di Fisica Sanitaria Ospeda1e Borgo Trento 37134 Verona, Italy

Dr. Giuliana Galli Alfa Wassermann S.p.A. via Ragazzi del '99 n.5 40133 Bologna, Italy

Dr. Maria Angela Girometta Camillo Corvi S.p.A. Stradone Faroese 118 29100 Piacenza, Italy

Prof. Gulin Guvendik Department of Toxicology Faculty of Phannacy University of Ankara 06100 Tandogan - Ankara, Turkey

Dr. Giorgio Iervasi CNR Fisiologia Clinica via Savi 8 56100 Pisa, Italy

S. K. Jain Institut flir Phannakologie Toxikologie und Phannazie Tierarzliche Hochschule Biintweg 17 3000 Hannover 771, Germany

Dr. Anupam Kaur School of Life Sciences Guru Nanak Dev University Amritsar-143 005, India

Dr. Daniel R. Krewski Biostatistics and Computer Applications Environmental Health Center Tunney's Pasture Ottawa, Canada

Dr. Ole W. Krogsgaard . . Dept. Clin. Physio!. & Nuclear Medicme University Hospital 9 Blegdamsvej DK-2100 Copenhagen 0, Denmark

Dr. Helen O. Kwanashie Department of Phannacology and Clinical Phannacy Faculty of Phannaceutical Sciences Ahmadu Bello University Zaria, Nigeria

Dr. Frank Larsen The Royal Danish School of Phannacy Dept. of Biological Sciences Pharmacology and Toxicology 2 Universitetsparken DK-2100 Copenhagen, Denmark

Dr. Michel Lemaire SandozAG Phanna Division Bau 507/801 . CH-4002 Bas1e, Switzerland

Dr. Jean Logan Department of Chemistry Brookhaven National Laboratory Upton, NY 11973, U.S.A.

Marie-Yvette Madrid Department of Che~cal Engineering Massachusetts InstItute of Technology Cambridge, MA 02139, U.S.A.

Vitus Malerczyk HoechstAG Klinische Forschung Abteilung fUr Biometrie und Dokumentation Postfach 80 03 20 6230 Frankfurt am Main 80, Germany

Prof. Giuliano Mariani C.N .R. Fisiologia Clinica via Savi 8 56100 Pisa, Italy

Dr Bernard M. Maziere Se~ice Hospitalier "Frederic Joliot" Hopital D'Orsay Orsay, France

Dr. Nicola Molea Servizio di Medicina Nuc1eare Clinica Medica II Universita di Pisa Pisa, Italy

429

Dr. Paolo Morazzoni Laboratorio di Fannacocinetica Inverni della Beffa via Ripamonti 99 20141 Milano, Italy

Prof. Amparo Sanchez Departamento de Fannacia A vda. del Campo Charro b/n 37008 Salamanca, Spain

Dr. Ronald J. Sawchuk Dr. Joyce Mordenti Clinical Phannacokinetics Laboratory Genentech, Inc. University of Minnesota 460 Point San Bruno Blvd. 308 Harvard Street S.E. South San Francisco, CA 94080, U.S.A. Minneapolis, MN 55455, U.S.A.

Dr. Sabine Ott Sandoz Phanna AG Human Phannacology Department Drug Safety Assessment Building 386/0ffice 956 CH-4002 Basle, Switzerland

Dr. Hilal Ozgunes Ziya Gokalp cad. 78/3 06600 Ankara, Turkey

Prof. Pietro Pavoni V Clinica Medica Policlinico Umberto I 00100 Roma, Italy

Prof. Jose Luis Pedraz Departamento de Fannacia A vda. del Campo Charro b/n 37008 Salamanca, Spain

Prof. Aldo Rescigno School of Pharmacy University of Panna Via Massimo d'Azeglio 85 Panna, Italy

Dr. Lillian E. Riad Department of Phannaceutics College of Phannacy University of Minnesota 308 Harvard Street S.E. Minneapolis, MN 55455, U.S.A.

Prof. Malcolm Rowland Department of Phannacy University of Manchester Oxford Road Manchester M13 9PL, U.K.

David Saldana Dep. de Quimica Inorganica y Analisis E.T.S.I.I. Univ. de Valladolid Valladolid, Spain

430

Dr. David E. Schafer Veterans Administration Medical Service West Haven, CT 06516, U.S.A.

Dr. Enrico Seccamani Sorin Biomedica S.p.A. via Crescentino 13040 Saluggia (VC), Italy

Dr. Thomas Skripsky Ciba-Geigy Corp. Dept. AG2.51 CH-4002 Basel, Switzerland

Dr. James T. Stevens Director of Toxicology Ciba-Geigy Corp. 410 Swing Road Greensboro, NC 27409, U.S.A.

Dr. Alberto Tajana Recordati Industria Chimica via M. Civitali 1 20148 Milano, Italy

Prof. Bernard Testa Ecole de Phannacie Universite de Lausanne place du Chateau 3 1005 Lausanne, Switzerland

Dr. Ajit K. Thakur Hazleton Laboratories America 9200 Leesburg Turnpike Vienna, VA 22180, U.S.A.

Dr. Alessandra Torroni Ellem Industria Fannaceutica viale dell'Industria 15/17 20094 Corsico (MI), Italy

Dr. Francis L. S. Tse Sandoz AG, Ph anna Division Bau 507/909 CH-4002 Basle, Switzerland

Prof. Isik Tuglular E. U. Tip Fakultesi Fannakoloji Anabili Dall, Bornova - Izmir, Turkey

Prof. Frantisek Vitek Inst. Biophysics & Nuclear Medicine Charles University, Salmovska 3 12000 Prague 2, Czechoslovakia

Prof. Nevin Vural Department of Toxicology Faculty of Phannacy University of Ankara 06100 Tandogan, Ankara, Turkey

Dr. Lauren Zech Laboratory of Theoretical Biology Building 10, Room 4B-56 National Institutes of Health Bethesda, MD 20892, U.S.A.

431

AUTHOR INDEX

Andersen, Melvin E., 203, 335

Balant, L. P., 281, 391

Balant-Gorgia, A.E., 391

Beck, James S., 27

Bocchialini, Bianca Maria, 1

Brill, A. Bertrand, 125

Buri, P., 281

Burnett, R. T., 53

Delforge, J., 169

Doelker, E., 281

Eichelbaum, M., 271, 391

Eiseman, Julie L., 69

Evans, Allan M., 83

Ferrante, Luigi, 189

Fischman, Alan J., 149

Gex-Fabry, M., 391

Green, James D., 411

Gross, A.S., 271

Karellas, Andrew, 125

Krewski, D., 53, 355

Krishnan, Kannan, 203, 335

Ku, L.F., 355

Mariani, Giuliano, 189

Maziere, B., 169

Maziere, M., 169

Mordenti, Joyce, 411

Parthasarathi, Arvind, 301

Rescigno, Aldo, 1, 189

Ross, W., 53

Rowland, Malcolm, 83

Rubin, Robert R., 149

Schafer, David E., 103

Stevens, James T., 315

Strauss, R. William, 149

Sumner, Darrell D., 315

Syrota, A., 169

Tajana, Albert, 227

Testa, Bernard, 257

Thakur, Ajit K., 41, 301

Travis, C. C., 355

Withey, J.R., 355

433

SUBJECT INDEX

Abbot's criterion, 306 Absorption, 1, 232 Acenocumarol, 239 Acetaminophen, 324 Acetylsalicylic acid, 284 Acetyltransferase, 392,401 Acquired immunodeficiency

syndrome, see AIDS Activase, 420 Activation, 233 Active moiety, 281 Adenocarcinoma, 71, 193 Adreamycin, 284 Adrenergic,182 Agarose, 284 AIDS, 76, 411 Albumin receptor, 92 Albumin-mediated uptake, 92 Aldose reductase inhibitors, 164 Allometric equations, 43, 414 Allometry, 203 Alpha-fetoprotein,190 Amiflamine, 393 Amitriptyline, 393 Ampicillin, 284, 294 Analog-to-digital converters, 129 Analytic statements, 27 Angiotensin converting enzyme

inhibitors, 157 Animal-human extrapolation, 337 Antiarrhythmic drugs, 271 Antidepressants, 180 Antimicrobial agents, 153, 163 Antineoplastic agents, 69, 155, 174 Antipyrine, 94, 140 Antispasmotics, 163 Antiviral agents, 69 Archimedes, 103

Area under the curve, see AVC Arylpropionic acid, 235, 237

derivatives, 275 Aspirin, 281 Asymmetric induction, 262 Asymmetric molecule, 229 Atenolol, 227, 235 Atrazine, 325 AVC, 5, 22, 70, 96, 209, 222 Autoradiography, 125 Avidin-biotin technique, 165 Axial dispersion model, 86 AZT, see Zidovudine

Bacampicillin, 284, 294 Bambuterol, 283 Barbiturates, 94 Benoxaprofen,238, 245, 275 Benzene, 361, 374 Benzodiazepine, 180, 182, 260 Beta-adrenergic receptors, 114 Beta-blocking drugs, 272 Bilirubin, 260 Bioavailability, 17,240,276,294 Biodistribution, 190 Blood pool imaging, 160 Blood volume, 161 Blood-brain barrier, 156, 174 Brain blood flow, 140 Bromobenzene,325 Bufuralol, 392, 399 Butene, 228

Candida Albicans, 155 Captopril, 157, 162 Carbamazepine,262 Carbenicillin, 285 Carbon tetrechloride, 373

435

Carboplatin, 69, 71 Carcino-embrionic antigen, 190 Carcinoma, 71 Cardiac output, 161,366 Carfecillin, 285 Carfentanil, 182 Carprofen, 238, 241 Carrier moiety, 281 CD4,416 Cefotiam, 285 Cell turnover rates, 131 Cellulose, 284 Cephalexin, 235 Cephalosporins, 285 Charge coupled devices, 128 Chiral discrimination, 258 Chiral drugs, 271 Chiral recognition, 258 Chirality, 228 Chloramphenicol, 283, 285 Chlordecone, 375 Chloroquine, 238 Chlorpromazine, 181 Cidoprofen, 238, 275 Cimetidine, 245 Cis-isomer, 228 Cisplatin, 71, 143 Clearance, 22, 204, 240, 289 Clomipramide, 393, 396 Clozapine, 182 Co-diffusion, 93 Codeine, 286, 393 Coding of experimental data, 11 Collisional limit, 112 Compartment, definition of, 11 Compartmental analysis, 3, 9 Compartmental equations, 10 Compartmental model, 2, 38, 54 Compartments, physiological, 356 Competing toxicity, 312 Competitive interaction kinetics, 106 Computed tomography, 128 Configuration, 229 Configurational isomers, 257 Conformation, 229 Conformers, 257 Constitutional isomers, 227 Contingency table, 302 Convolution, 6, 88 Cooperativity factor, 47 Cornfield's model, 305 Creatinine clearance, 75 Cumarin anticoagulants, 234 Cumene, 266 Cycloexane, 228

436

Cyclophosphamide, 287 Cytotoxic agents, 69

Debrisoquine, 238, 392, 393, 399, 401

Decanoic acid, 282 Deconvolution, 88 Dedrick plot, 209 Densitization, 114 Deoxyfluorouridine, 286 Deoxyglucose brain uptake, 174 Deprenyl,181 Dermal absorption, 341 Desipramine, 396 Dextran, 284 Dextro-isomer, 229 Dextromethorphan, 393 Diagnostic plot, 60 Diastereoisomer, 230 Diastereomer, 230, 257 Diazepam, 85,95,402 Dichloroethylene, 372 Dichloromethane, 343 Diclofenac, 92 Diffusion-limited association, 106 Digitalis Purpurea, 231 Digitoxin, 231 Dimensionless variables, 36 Dimethylcyclopentane, 228 Dinitrophenol, 112 Dioxane, 327 Diphenylhydantoin, 174 Disopyramide, 234, 238, 245 Dispersion number, 86 Distomer, 176,231,271 Distributed sinusoidal model, 86 Distribution, 1, 217, 235 Dobutamine, 272 Dopa, 235 Dopamine receptors, 157 Dopamine, 117 Dopaminergic, 182 Dose selection, 415 Dose-response assessment, 335 Down-regulation, 114 Doxifiuridine, 286 Doxorubicin, 91 Drug labelling, 169 Drug-receptor interaction, 108, 175 Dual tracer autoradiography, 142

Effluents, 103 Ehrlich, 103 Eigenvalues, 2 Elimination, 1

Empedocles, 103 Empirical model, 42 Enalaprilat, 91 Enantiomers, 227, 257, 271 Enantioselectivity, 259 Encainide, 393 Endismic ratio, 240 Endocytosis, 115 Enzyme inactivation, 341

induction, 341 Eosin, 133 Epidermal growth factor, 115 Epimers, 231 Erythrocytes, 36 Erythromycin, 153, 174 Erythrose, 230 Estrogen, 182 Estrone, 284 Ethanol, 227 Etilefrine, 285 Etodolac, 235 Eudismic ratio, 231 Eudragit, 285 Eutomer, 176,231,271 Exachlorobiphenyl,375 Excretion, 238 Exposure assessment, 335

levels, 220

Fact and meaning, 32 Fenoprofen, 238, 241, 275 Fibonacci scheme, 90 Fitting of experimental data, 32,39 Fitting pharmacokinetic models, 57 Flecainide, 393 Flip-flop kinetics, 288 Flopenthixol, 282 Flow cytometry, 134 Fluconazole, 150, 155 Flumazenil, 180 Flunitrazepam, 180 Fluorescence-activated cell sorter, 134 Fluoro uracil, 156 Fluoroquinolones, 158 Flupenthixol,182 Fluphenazine, 157, 282 Flurbiprofen, 238, 241 Folinic acid, 233 Fruorouracil, 285, 286, 340 Fumaric acid, 228

G proteins, 113 Galactose, 85 Gamma model, 303 Gauss-Newton iterative procedure, 58

Gaussian estimation, 53, 58 GAZT,77 General product model, 304 Gentisamide, 91 Glomerular filtration, 75, 218 Glucose uptake, 140 Glutathione, 341 Glyceraldehyde, 228

Half-life of a drug, 3, 204 Halogenated hydrocarbons, 375 Haloperidol, 117, 182 Hartley-Sielken model, 304 Hazard identification, 335 Hematoxylin, 133 Henoglobin, 108 Hepatic clearance, 210 Hepatic dispersion, 87 Hepatic drug elimination, 83 Hepatobiliary agents, 163 Hepatocyte, 89 Heptachlor, 309 Heroin, 287 Heteroscedastic errors, 54 Heteroscedasticity, 60 High dose-low dose extrapolation,

336, 338 High performance liquid chromato-

graphy, see HPLC HIV, 69, 416 Hormesis, 312 Horse radish peroxidase, 135 HPLC, 137,199

enantioner resolution by, 247 Human equivalent dose, 305 Human Immunodeficiency virus, see

HIV Human serum albumin, 89 Hydrolysis of internalized ligand, 115 Hydroxypropylcellulose, 284

Ibuprofen, 234, 238,241,245, 275, 287

Image acquisition, 128 Imaging technology, 125 Imipramine, 180, 393 Immunohistochemistry, 143 Immunoscintigraphy, 189 Indoprofen, 235, 238, 241 Indoramin, 393 Inhalation, 55 Insulin, 284

receptor, 108, 114 Interspecies extrapolation, 339

. Interspecies scaling, 43,203,412

437

Intravenous injection, 341 Inulin, 284 Invariant quantities, 1 Iputerol,283 Isomers, 227 Isoniazid, 395

Kepone, 375 Kernel smoothing of data, 53 Ketoprofen, 238, 245

L-dopa, 174 Labetalol, 231 Lactam, 235 Laplace transform, 88 Laser confocal microscope, 127, 134 Law, 27 Least squares, 42 Lethal dose, 45 Leukemia, 71 Levo-isomer, 229 Levopromazine, 182 Lidocaine, 85 Ligand-receptor binding, 47 Ligands, 103 Limits of the model, 32 Linearized multistage procedure, 336 Liver cirrhosis, 274 Logistic model, 45 Logistic model, 303 Logit model, 45, 303 Low dose risk assessment, 378 Lumped parameters, 49

Magnetic resonance imaging, 149 Maleic acid, 228 Mannich bases, 283 Marquardt algorithm, 195 Matrix equation, 16 Maximum concentration, 2 Maximum lifespan potential, 204,211 Maximum likelihood method, 42, 46,

53,60 Maximum tolerated dose, 70,315 Mechanistic model, 42, 302 Mecillinam, 285 Melanocyte-stimulating hormone, 108 Melanoma, 71 Meperidine, 85 Mephenytoin, 394, 402 Mepivacain, 235 Metabolic clearance, 217 Metabolic inhibition, 265 Metabolism, 235 Metadone, 248

438

Methotrexale, 235,211,340,377 Methyl ether, 227 Methyl-spiperone, 117 Methylchloroform, 373 Methyldopa, 282, 285 Methylene chloride, 343, 361, 369,

371, 380 Methylmercury, 53 Methylumbelliferone, 90 Metoprolol, 238, 242, 248, 393, 395,

400 Michaelis-Menten

analysis, 264 equation, 361 estimation, 53

Microparameters,14 Microspheres, 140 Misonidazole, 142 Mitomycin, 284 MLAB computer program, 73 Model, 27, 41

and experiment, 28 and experimental data, 31 validation, 370

Model-free analysis, 39 Model-independent parameters, 22 Modeling, 13 Modulation

of experimental data, 11 transfer function, 127

Moments, 18, 19, 21 Monoclonal antibodies, 189 Moolgavkar-Venzon-Knudsen model,

348 Morphine, 231, 287 Multi-hit model, 303 Multiple time analysis plot, 172 Multistage

model,302 procedure, 336

Muscarinic, 182

Nalbuphine, 282 Naltrexone, 182,285 Naproxen, 241, 275, 284 Neoteny, 204, 211 Neuroleptics, 156, 181 Nicotine, 245, 261

acetylcholine receptor, 109 Nicotinic acid, 284 No observable effect level, see

NOAEL NOAEL, 315, 337 Non-compartmental parameters, 22

Non-steroid anti-inflammatory agents, 234

Nonlinear kinetics, 399 Nonlinear regression model, 59 Nonparametric estimation, 53 Nortriptyline, 393, 396 NSAI agents, 284 Nuclear magnetic resonance, 128,

157, 163

Objective function, 58 Omeprazole, 286 One-hit model, 302 Opioid,182 Oral gavage, 341 Oxazepam, 258, 243

PAP technique, 135 Papaver Somniferum, 231 Paracelsus, 315 Parachloroamphetamine,245 Paradigm shift in biology, 118 Parameter optimization, 370 Parsimony, 38 Partition coefficient, 219, 340,366 Paucimolecular membrane model, 49 Penetration, 235 Pentobarbital, 234, 263 Pep tides, 285 Percholoethylene,372 Perhexiline, 393 Permanence time, 16 Permeability, 89 Perphenazine, 393 PET, 117, 149, 169 Pharmacodynamics, 159 Pharmacogenetics, 391 Pharmacokinetics, 190 Phase I trials, 90 Phenformin, 393 Phenotyping, 394 Phenylacetate,43 Phenylbutazone, 244 Phosphoramine mustard, 287 Phosphorilation, 114 Physiologic models, 83,212 Physiological time, 207 Pimozide, 181 Pindolol,238 Pivampicillin, 285, 294 Pivmecillinam, 285 Platelet count, 95 Platelets, 112 Platinum compounds, 156 Plychlorinated biphenyls, 375

Positron emission tomography, see PET

Positron emitting radionuclides, 169 Power law, 38 Practolol, 227 Precolumn derivatization, 247 Precursor, 6

order, 8 Predator-prey equation, 43 Prediction, 42, 49

and retrodiction , 32 Primary system, 41 Primisulfuron, 323 Probit model, 46, 303 Procainamide, 284 Prodrugs, 281 Product stereoselectivity, 261 Progesterone, 285 Propafenone,393,404 Propericiazine, 182 Propranolol, 85, 91, 234, 235, 242,

247,260,271 Propylajmaline, 393 Protein binding, 92, 341 Pubivacaine, 235 Pyrene,63

Quinidine, 239, 400 Quinine, 239

Racemates, 227, 230, 271 Raclopride, 117, 156, 180, 182 Radioactive decay, 9 Radiochemistry, 181 Radioimmunoassay, 47, 169 Receptor cooperativity, 107 Receptor internalization; 115 Receptor turnover, 115 Receptor-mediated internalization, 114 Recognition, 235 Reference dose, 337 Regression methods, 53 Renal clearance, 211 Renal perfusion, 162 Residence time, 16, 144

distribution, 86 Retrodiction, 42, 49

and prediction, 32 Risk assessment, 224 Risk characterization, 335 Robust estimation, 53 Root-root extrapolation, 339 Rutherford equations, 9

Safety factor, 305

439

Salicylamide, 285 Salicylic acid, 281 SAS statistical analysis package, 60 Saturation kinetics, 379 Saturation, 312 Scaling, 218

of physiologic parameters, 368 Scatchard equation, 47 Secondary system, 41 Sequestration, 114 Serine, 229 Serotinergic, 182 Sesipramine, 393 SIGNS, 231 Simazine, 321 Simulation, 13 Simulator, 29 Single photon imaging, 149 Sorbinil, 164 Sparteine, 392 Spiperone, 172, 182 Spline functions, 34 Staining technology, 133 Starch,284 Statistical regression, 13 Steady-state availability, 96 Stereoisomerism, 271 Stereoisomers, 227, 257 Stereoselective drug disposition, 272 Stereospecificity, 186 Stewart-Hamilton principle, 6 Stochastic compartmental models, 53 Stochastic models, 86 Styrene, 55, 340, 371 Substrate stereoselectivity, 261 Successor, 6 Sulfinpyrazole, 322 Sulindac,287 Sulpiride, 1182 Suriclone, 180, 184 Synchrotron light sources, 128 Synthetic statements, 27 System analysis, 41

Talamolol, 393 Talampicillin, 285 Talidomide, 235 Tank-in-series model, 86 Tartaric acid, 231 Tauracholate, 92, 95 Terbutaline, 235, 245, 283 Testosterone, 284 Tetrachlorodibenzodioxin, 376 Tetrachlorodibenzofurans, 376 Theophilline, 158

440

Theory, 28 Therapeutic window, 244 Thermoluminescent rod, 144 Thiethyperazine, 182 Thioproperazine, 182 Thioridazine, 393 Thioxaprofen, 238, 275 Threose, 230 Threshold, 311 Thrombocytopenia, 74 Thymidine, 76, 141 Tiaprofenic acid, 238 Time-to-tumor model, 304 Timolol, 393 Tissue dosimetry, 379 Tocainide, 241 Tofisopam, 260 Tolerance distribution model, 303 Tomographic images, 126 Torpedo Californica, 109 Tranquillizers, 180 Trans-isomer, 228 Transfer function, 6 Transfer time, 6 Transit time, 14 Transition probability, 11 Trichloroethylene, 372, 381 Tumor-associated antigens, 189 Turnover rate, 8 Turnover time, 14

Undistributed parallel-tube model, 85 Uptake, 206, 216 Uses and limits ofthe model, 32

Van der Graaf accelerator, 140 Ventricular function, 159 Verapamil, 235, 242, 245,248,273 VEST (Ventricular function monitor),

160 Vinyl chloride, 326 Viscoleo, 282 Volume of distribution, 1,204,210

VVarfarin,90,92,237,244,245,275 VVeibull model, 304 VVeighted least squares, 53 VVell-stirred model, 84 VVholebody pharmacokinetics, 98

Xenobiotic agents, 53

Zidovudine, 69, 76 Zonation, 91 Zuc1opentixol, 282