Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 477
Index
A
Absorption
extrapolation of, 139- 140
gastrointestinal, 122
rate of, 121
skin, 122-123
ACSL language, 232-233
Adenine arabinoside model, 58
Adenomas, hepatocellular, 459
Administered and delivered doses,
330, 447-455
ADSIM language, 232
Air, excretion into, 142- 143
Allometric equations, 66-67
Allometry, 65-78
valid and invalid extrapolations of,
141
Allyl chloride, 176-179
Alveolar space mass-balance equation,
262
Anatomical models, lower respiratory
tract, 305-307
Angiosarcomas, 456-457
Animals
no-observable-effect levels (NOELs)
for, 4-5
477
pharmacokinetic studies in, 407-
408
polymorphisms in, 146
Anticancer therapy, prospective
predictions and validations in, 431-
440
Apparent volume of distribution, 31
Area under tissue curve (AUTC), 11
Areas under concentration-time curves
(AUCs), 256, 471-472
Armitage-Doll multistage model, 443
Arterial blood mass-balance equation,
262
AUCs (areas under concentration-time
curves), 256, 471-472
AUTC (area under tissue curve), 11
Availability, systemic, 453
Average concentration, 97
Axial dispersion number, 87
B
BASIC language, 231-232
Bayesian methods, 190
Bile
excretion, 116, 122, 142-143
duct mass-balance equation, 53
OCR for page 478
478 INDEX
Binding
affinity, 14
drug, 88-89
plasma, 90
tissue, 90
Bioavailability
fraction of dose absorbed and, 122
gastrointestinal absorption and, 122
skin absorption and, 122-123
Birth rate for cells, 380
Blood
carboxyhemoglobin, 169
pool mass balance, 46-47
Body
clearance, total, 108, 115
mass dependent metric, 70-73
regions, 39-44
size, in pharmacokinetic models,
65-78
weight (BW), 18- 19, 209
Bolus administration, 43
C
C language, 231
Cancer model, two-stage, 21
Carbon dioxide mass-balance
equation, 263
Carbon monoxide mass-balance
equation, 263
Carbon tetrachloride, model for, 312-
324
Carboxyhemoglobin, blood, 169
Carcass mass-balance equation, 262
Carcinogens and carcinogenesis
chemical, quantitative risk
assessment for, 6
DNA adducts and, 221-226
epigenetic, 16, 20-22
genotoxic, 16
inhibitors of, 222
models of, 443
multistage model of, 463, 467-468
risk assessment, 441-445
Carcinomas, hepatocellular, 371, 459
CCSL IV language, 232
Cell birth versus mutation
accumulation, 277
Chronic bioassay, 6
Chronological time, 69, 73
Circulation time, mean, 41
Classical pharmacokinetics, 34-35, 37
Clearance, 17
hepatic, 125- 126
interface between PB-PK models
and, 104-107
metabolic, 102
mucociliary, 329
renal, 128-131
total body, 108, 115
value, 81
Closed-chamber kinetics, 170, 172
Cofactor depletion, dose-dependent,
135-137
Compartments
choice of, 39-44
deep, 195
linear models of, 104, 105
multicompartments, see
Multicompartment model
one, see One-compartment model
three, see Three-compartment model
two, see Two-compartment model
Complexes, rates of formation of, 98-
99
Computational
equipment needs, 233-234
resources, sharing, 246
Computer languages used in
pharmacokinetic model, 230-232
see also specific languages
Concentration
-dependent metabolite elimination,
134-135
gradient, 27
models, versus experimental, 268-
270
-time curves, areas under (AUCs),
256, 471-472
-time data, 185
Confidence regions, 190- 191
linear, 200, 202
OCR for page 479
INDEX 479
Contour plots, 200-202
Covalent binding, 11
Critical
exposure time, 435
toxicity reference (CTR) system,
354-357, 363-365
Curvilinear dose response, 448-450
Cytochrome P-450 isozymes, 148
Cytosine arabinoside pharmacokinetic
model, 57-58
Cytotoxicity
-hepatic, 275
modeling of, 273-279
mutation acumulation and, 273-283
D
DCM (dichloromethane) (methylene
chloride), 171-172, 217-219,
254-264, 392-408, 458-462
De minimus value, 155
Death rate for cells, 380
Dedrick plot, 74-75
Deep compartment, 195
Delivered and administered doses,
330, 447-455
Depletion, 11
cofactor, dose-dependent, 135- 137
glutathione, 175- 177, 178, 179
Detoxification, 452-453
Dibromomethane concentration, 168
Dichloromethane (DCM, methylene
chloride), 171-172, 217-219,
254-264, 392-408, 458-462
Diffusion, 28
barriers, 99-102
index, 100
through thick membranes, 122-123
Direct decoupled method, 189
Dispersion number, axial, 87
Distribution
intraorgan, extrapolation of, 140-
141
rate constants, 141 - 142
volume of, see Volume of
distribution
DNA adducts, 221-223
Dose/dosage, 471
administered and delivered, 160,
330, 447-455
dependencies, 120- 139
escalation, 433
extrapolations, 120-125, 170, 172-
173
fraction of, absorbed, 122
-incidence of response curve, 150-
151
log, versus percentage response, 4
low, risks at, 327-328, 444-445
-magnitude of response curve, 150-
151
maximum tolerated (MTD), 6, 432-
433, 449, 450
principle of fraction of, 128-131
response, 3-4, 221, 225-226, 375-
376, 448-450
-route extrapolation, 165- 167, 168,
216-219
safe starting, 433
scaling, 416-419
scheduling, 420-425,
surrogates, 293-295
time-dependent, 467-468
time-weighted average, 454
virtually safe (VSD), 296-298
Dosimetry models, 230
comparisons, interspecies, 361-363
hazard assessment using, 353-367
lower respiratory tract mathematical,
357-363
physiologically based, 354-357
Drinking water exposures, modeling,
401-406
Drug
binding, 88-89
development, 432-433
disposition, 43
solubility, 89-90
transport, 89-90
OCR for page 480
480 INDEX
E
EAI Pacer 500 analog-digital hybrid
computer, 335, 336
EDC (ethylene dichloride), 288-300
Efficiency number, 87
Elimination
by excretion, 142- 143
half-life of, 30
location of organs of, 116-117
by metabolism, 143-148
organs, 83-86, 109, 112- 114
pulmonary, 385-387
rate constant, 28
species differences in, 142-148
Emphysema, 354
Endogenous precursors, 136
Energetics of muscle, 68-69
Environmental risk assessment, 431
Enzymes
idealized distribution of, 127
inhibition, suicide, 173- 175
intraorgan localization of, 126- 128
Epigenetic carcinogens, 16, 20-22
Equilibrium constants, 99
Error analysis in model building, 188-
193
Ethical considerations, 431
Ethylene dichloride (EDC), 288-300
Exact method, l 90
Excess lifetime cancer risks, 6
Excretion
biliary, 116, 122
elimination by, 42-143
Exercise, ozone uptake and, 308-310
Experimental error, 191 - 193
Exposure(s) 471
assessment, 8-9
drinking water, modeling, 401-406
intravenous injection, modeling, 406
scenario, extrapolation, 161, 167-
168, 169
time, critical, 435
time-dependent, see Time-dependent
exposure
Extraction ratio, 82, 85, 105
hepatic, 84
mathematical solution for, 87
Extrapolation, 312, 441-442
in absorption of substances, 139-
140
of allometric methods, 141
dose, 120-125, 170, 172-173
dose-route, 165-167, 168, 216-219
exposure scenario, 161, 167-168,
169
four types of 159
general aspects of, 96-155
from in vitro systems, 80-93
of interorgan distribution of
substances, 140-141
interspecies, 212-216, 441-442
low-dose risk, 327-328, 444-445
pharmacokinetic, 161-162
physiologically based models for,
159-180
route-to-route, 114-119
species-to-species, 139- 142, 168-
170, 171, 396-401
F
F-Ara-AMP (fludarabine phosphate),
437-438
Fat group (FG) of organs, 447
Feathering process, 29
Fick's First Law, 27, 32-33
Fick's Law of Diffusion, modified,
99-102
First-order rate constants, 90
First-pass
elimination organs, 114
nonelimination organs, 113- 114
organs, 109
Flexible polygon method, 189
Flow
diagrams, 40, 42
-limited models, 48-49, 446
rate, 32
Fludarabine phosphate (F-Ara-AMP),
437-438
Formaldehyde, 455-456
OCR for page 481
INDEX 481
linear proportionality and, 328-330
FORTRAN programs, 230-231
Fraction of dose principle, 128-131
Free intrinsic clearance, 82
G
Gas-uptake behavior, 175-177
Gastronintestinal absorption, 122
Gavage risk, 375-379
(;enotoxic carcinogens, 16
Glutathione
depletion, 175-177, 178, 179
-S-transferase (GST) path, 459-462
Graphic output, 234
GST (glutathione-S-transferase) path, Inhibitors
459-462
Gut mass-balance equations, 53-54,
261
H
Half-life, 28, 31
of elimination, 30
minimum, 106
of terminal phase, 106
Half-time to approach maximum
concentration, 99
Hazard assessment, 8-9
using dosimetry modeling approach,
353-367
Hepatic
clearance, 125- 126
cytotoxicity, 275
extraction ratio, 84
Hepatocellular
adenomas, 459
carcinomas, 371, 459
Heteroscedasticity parameter, 193,
195
Humans
inhalation, 216, 217
murine toxicity and, 434-435
no-observable-effect levels (NOELs)
for, 5
polymorphisms in, 146-147
risk assessment, 369-370
Hybrid rate constants, 106
N-Hydroxy arylamines, urinary
bladder exposure to, 334-348
I
In vitro systems, extrapolation from,
80-93
Inaccuracy, degree of, 149
Inducers, 144-145
Inhalation
model, 165- 167
risk, 375-379
of carcinogenesis, 222
suicide, 137- 139
Initiation index, 224
Intercalating agents, 19-20
Interspecies
differences, 153- 155, 330-331
dosimetric comparisons, 361-363
extrapolation, 212-216, 441 -442;
see also Extrapolation
scaling, 16- 19, 36
. . .
ntravenous 1nJectlon exposures,
modeling, 406
Intrinsic clearance, 81-82
Isometry, 66
Isozymes, 143-144
cytochrome P-450, 148
interstrain differences in, 145- 146
J
Joint risk assessment, 5
Judgmental decisions, 208
K
Kidney
mass-balance equation, 52, 262
partition coefficients, 91
OCR for page 482
482 INDEX
Kinetic
models, see Pharmacokinetic models
rate constants, 31
Kleiber equation, 66
Kliment zone model, 307
L
Law of Mass Action, 149
Lawrence Solver for Ordinary
Differential Equations (LSODE),
190
Lifetime cancer risks, excess, 6
Likelihood
estimates, 188- 190
function, 188, 195
~ . .
Llnearlty
compartment models, 104, 105
detoxification, 452-453
kinetics, 450
low-dose, 444
proportionality, formaldehyde and,
328-330
steady-state models, 117-118
Lineweaver-Burk plots, 192
Literature evaluation, 15
Liver
mass-balance equation, 53, 261
partition coefficients, 91
Low dosage
linearity, 444
risk extrapolation, 327-328, 444-
445
versus percentage response, 4
Lower respiratory tract (LRT)
anatomical models, 305-307
mathematical dosimetry modeling,
357-363
ozone absorption in, 302-310
Lung
administration, 115
dosimetry model, 235
mass-balance equation, 261-262
partition coefficients, 91
M
Mammals, flow diagram for, 40
Mass action law, 20
Mass balances, 44
basic, 44, 46-47
blood pool, 46-47
equations for, 14, 51-54, 261-263
simplifications of, 47-56
tissue regions, 47, 48
Mass-specific rates, 73-74
Mathematical pharmacokinetic
models, 445-446
Maximum
concentration, 97, 99, 112
tolerated dose (MID), 6, 432-433,
449, 450
velocity of reaction, 14
Mean circulation time, 41
Membrane
-limited model, 446-447
diffusion through thick, 122-123
permeability, 48-49
resistance, 41
Metabolism
clearance, 81, 102
dose-dependent changes in, 125-
139
elimination by, 143-148
interorgan differences in, 145
interspecies differences in, 147-148
pathways, 14
production, 19
rate constants, 212, 288-290
role of, 392-396
sex differences in, 144
strain differences in, 143-144
urinary, 147
Metabolites
concentration of, 120
elimination, concentration-
dependent, 134- 135
formation and elimination of, 117-
118
functional classification of, 118
reactive nonisolatable, 17, 19
OCR for page 483
INDEX 483
stable, 17, 18, 119
unstable, 119
Method of residuals, 29
Methotrexate (MIX), 410-425
pharmacokinetic model of, 53-56
Methylchloroform, 392-408
Methylene chloride (dichloromethane,
DCM), 171-172, 254-264, 392-
408, 458-462
MFO (mixed-function oxidase) path,
459, 461
M-ice, old, 407-408
Michaelis-Menten kinetics, 81-83,
125-126
Microcomputers, 231-232, 234
Minimum
concentration, 97, 112
half-life, 106
Mitotic rate, 380
Mixed-function oxidase (MFO) path,
459, 461
Models
adenine arabinoside, 58
Armitage-Doll multistage, 443
anatomical, lower respiratory tract,
305-307
building, 187, 188- 193
cancer, two-stage, 21
carcinogenesis, 443
compartmental, 162
cytotoxicity, 274-277
dosimetry, see under Dosimetry
drinking water exposures, 401-406
flow-limited, 446
inhalation, 165- 167
intravenous injection exposures, 406
kinetic, see Pharmacokinetic models
Kliment zone, 307
linear compartment, 104, 105
linear steady-state, 117-118
lung dosimetry, 235
mathematical, 445-446
membrane-limited, 446-447
multicompartment, see
Multicompartment model
multispecies multroute, 391-408
multistage, see Multistage model
one-compartment, see One-
compartment model
parallel tube, 86-87, 113
PB-PK, see Physiologically based
pharmacokinetic models
PBD, see Physiologically based
dosimetry model
perfusion-limited physiological, 82-
83
pharmacokinetic, see
Pharmacokinetic models
physiologically based, see
Physiologically based
pharmacokinetic models
sinusoidal perfusion, 86-87
steady-state, linear, 117- 118
three-compartment, see Three-
compartment model
two-compartment, see Two-
compartment model
two-stage carcinogenicity, 21, 273-
274
venous-equilibration, of organ
elimination, 83-86
well-stirred, of organ elimination,
83-86, 113
Moolgavkar-Knudson model, 276-277
MTD (maximum tolerated dose), 6,
432-433, 449, 450
MTX, see Methotrexate
Mucociliary clearance, 329
Multicompartment model, 29, 235-
239
Multienzyme system, 86
Multispecies multiroute models, 391-
408
Multistage model, 150
of carcinogenesis, 463, 467-468
Murine and human toxicity,
comparison of, 434-435
Muscle
energetics of, 68-69
group (MG) of organs, 447
mass-balance equation, 51
partition coefficients, 91
OCR for page 484
484 INDEX
Mutation accumulation
cell birth versus, 277
cytotoxicity and, 273-283
N
National Ambient Air Quality
Standards (NAAQs), 353-354
National Biomedical Simulation
Resource (NBSR), 233, 246-247
National Toxicology Program (NTP),
449
Nickel injection, 237-239
NOELs (no-observable-effect levels),
4-5
Nonelimination organs, 109- 114
Non-first-pass
elimination organs, 109, 112- 113
nonelimination organs, 109- 112
Nonlinear
kinetics, 104
method, 190
No-observable-effect levels, see
NOELs
NTP (National Toxicology Program),
449
o
Occupancy, 11
One-compartment model, 28-29, 55
Oral administration, 116
Organs
availability, 104
classification of, 108- 110
elimination, 83-86, 109, 112-114
first-pass, 109
grouping of, 447
location of elimination of, 116- 117
nonelimination, see 109- 114
non-first-pass, 109- 113
rapidly equilibrated, 109
slowly equilibrated, 109
Oxidative pathway, saturable, 266
Ozone
absorption in lower respiratory tract,
302-310
dosimetry modeling approach with,
353-367
exercise and uptake of, 308-310
uptake of, 360-363
p
P (probability), 151
Parallel tube model, 86-87, 113
Parent chemicals, 16- 17
Partition coefficients, 33, 89-90, 91,
288,317,446
Pascal language, 2231, 232
PB-PK models, see Physiologically
based pharmacokinetic models
PBD (physiologically based
dosimetry) model, 354-357
PCE (perchloroethylene), 210-217,
285-290, 369-382, 385-390,
462
Peeling process, 29
Percentage response, log dosage
versus, 4
Perchloroethylene (PCE), 210-217,
285-290, 369-382, 385-390,
462
Perfusion-limited physiological model,
82-83
Permeability, membrane, 48-49
Perspectives, 471-475
Pharmacokinetic (PK) models, 13, 36,
162, 229-230, 442
body size in, 65-78
building, 185- 193
classical, 34-35, 37
computer languages used in, 230-
232
conventional approaches to, 234-
235
. . . .
data in carcinogenic risk
assessment, 441-463
description of, 209-212
OCR for page 485
INDEX 485
for drinking water exposures, 401-
406
equipment needs for, 233-234
extrapolation, 161-162; see also
Extrapolation
flow chart of development of, 15
introduction, 27-35
mathematical, 445-446
objective of, 96
physiologically based, see
Physiologically based
pharmacokinetic models
for thiopental, 50-54
uncertaintly in, using SIMUSOLV,
185-207
Physiological time, 69-76
Physiologically based dosimetry
(PBD) model, 354-357
Physiologically based pharmacokinetic
(PB-PK) models, 13- 14, 36-59,
162-165, 273-274, 442, 446-
447, 472-475
abbreviations and symbols used in
specific, 211
for adenosine arabinoside, 58
biological basis of, 38-39
for carbon tetrachloride, 312-324
construction of, 385-390
for cytosine arabinoside, 57-58
description of specific, 209-212
development of, 39, 287-288
diagram of generic, 163
diagram of specific, 210
dose, species, and route
extrapolation using, 159- 180
for ethylene dichloride, 288-300
fundamental equation of, 33
general, 96-104
interface between clearance and,
104-107
of intravenous injection exposures,
406
limitations of, 282-283
linear, 107-113
linear compartmentalized, 104, 105
for methotrexate, 53-56, 414-416
Moolgavkar-Knudson, 276-277
multispecies multiroute, 391-408
in old aminals, 407-408
of ozone absorption in lower
respiratory tract, 302-310
for percholoroethylene, 285-290,
369-382
physiological and biochemical
parameters used in specific, 213
potential of, 35
Ramsey-Andersen, 274-275
risk assessment and, 295-296, 474
route-of-exposure differences and,
298
route-to-route extrapolation of
dichloromethane using, 254-264
schematic representation of, 287
sensitivity analysis in, 265-272
simple, 102-103
simplification of, 98
validation of, 283, 317-319
virtually safe doses and, 296-298
Plasma
binding, 90
mass-balance equation, 51
membranes, 100
Poly-input availability, 114
Ploymorphisms
in animals, 146
in humans, 146-147
Precursors, endogenous, 136
Predictions, prospective, in anticancer
therapy, 431-440
Probability (P), 151
Problem identification, 15
Prospective predictions in anticancer
therapy, 431-440
Pulmonary
fibrosis, 354
uptake and elimination, 385-387
Q
Quantitative risk assessment, for
chemical carcinogenesis, 6
OCR for page 486
486 INDEX
R
R parameter, 103-104
organ/blood, 141-142
Ramsey-Andersen PB-PK model,
274-275
Rapidly equilibrated organs, 109
Rate constants, 99, 106
distributional, 141- 142
hybrid, 106
metabolic, 212
metabolism, 288-190
Rats
ingestion by, 214-215
inhalation by, 212-214
old, 407
Reactive nonisolatable metabolites,
17, 19
Reactivity equations, chemical, 11
Receptor binding equations, 11
Reitz-Andersen optimization
procedure, 265-272
Renal clearance, 128- 131
Residence time, 139- 140
Residuals, method of, 29
Respiratory tract, see Lower
respiratory tract; Upper respiratory
tract
Response
dosage versus, 3-4
percentage, log dosage versus, 4
Risk assessment, 208
at low doses, 327-328, 444-445
carcinogen-DNA adducts in, 221-
226
carcinogenic, 441-463, 443-445
combination techniques, 7
elements of, 9
environmental, 431
extrapolation, low-dose, 327-328
historical perspectives, 3-7
human, 369-370
joint, 5
major elements of, 355
management, major elements of,
355
objective of, 471
PB-PK model and, 295-296, 474
quantitative, see Quantitative risk
assessment
tissue dosimetry in, 8-23
with time-dependent exposure
patterns, 453-455
Route-of-exposure differences, PB-PK
model and, 298
Route-to-route extrapolation, 114- 119
S
Safe starting dose, 433
Safety factor (SF), 5
Saturable
detoxification, 452-453
oxidative pathway, 266
Scaleup, see Extrapolation
Scaling
interspecies, 16- 19, 36
formulas, 209, 212
SCoP (Simulation Control Program),
232, 233
example program, 239-246
Semipermeable membranes, 100
Sensitivity analysis, 265-272
Sex differences in metabolism, 144
SIMNON language, 232
Simulation, 229
future trends in, 249
general approaches to, 229-230
languages, 232-233
in toxicology, 229-250
training in, 246
Simulation Control Program, see
SCoP
SIMUSOLV, 185, 186, 233
applications of, 193-205
statistical analysis using, 204
statistical output for, 206-207
uncertainty using, 185-207
Sinusoidal perfusion model, 86-87
Skin
absorption, 122- 123
administration, 115
OCR for page 487
INDEX 487
Slowly equilibrated organs, 109
Solubility of drug, 89-90
Species differences, 38-39
in elimination, 142- 148
Species-to-species extrapolations,
139-142, 168-170, 171, 396-
401
Stable metabolities, 17, 18, 119
Starting dose, safe, 433
Steady statefs)
concentration, 107, 118
- conditions, 98-99
distribution ratio, 288
models, linear, 117- 118
term, 107
virtual, see Virtual steady states
Suicide
enzyme inhibition, 173- 175
inhibitors, 137- 139
Surface area adjustment, 17-19, 160
Systemic availability, 453
T
TO (tracheobronchial) liquid lining,
357-361
Terminal half-lives, 106
Thiopental pharmacokinetics model,
50-54
Three-compartment model, 334, 336,
337
Threshold effect, 435-436
Time
chronological, 69, 73
integral of tissue exposure, 10
-dependent dosing, 467-468
-dependent exposure, 451-455
physiological, 69-76
-weighted average dose, 454
- weighted average receptor
occupancy, 20
, —-
~ssue
binding, 90
dosimetry in risk assessment, 8-23
exposure, time integral of, 10
mass balance, 48
partition coefficients, 91
perfusion, 49
regions, 45-47
total concentration, 49-50
volume, 19
Tolerated dose, maximum (MTD), 6,
432-433, 449, 450
Toxicity
assessment of, 410-425
comparision of human and murine,
434-435
mechanism of, 412-414
nonsaturable pathway, 266
Toxicology Information Network
(TOXIN), 247-248
Toxiphors, 265
Tracheobronchial (TB) liquid lining,
357-361
Transfer constant, 27
Transition rate, 380
Transport, drug, 89-90
Tumor promoters, 21
Tumorigenesis, 5-6
Two-compartment model, 30-31, 32,
43, 194
Two-stage carcinogenicity model, 21,
273-274
TYMNET data communications
network, 247
U
Unbound
concentration, 103, 108
fractions, 88-92, 103
Uncertainty~ies)
error analysis and, 188- 193
inherent, 473
using SIMUSOLV, 185-207
Unstable metabolites, 119
Upper respiratory tract (URT), 303
morphology of, 358
Urinary
bladder exposure to N-hydroxy
arylamines, 334-348
metabolism, 147
OCR for page 488
488 1 NDEX
Urine, excretion into, 142- 143
URT, see Upper respiratory tract
V
Validations
of PB-PK models, 283, 317-319
prospective, in anticancer therapy,
431-440
Variance of error, 191 - 193
VCM (vinyl chloride monomer), 456-
458
Velocity of reaction, minimum, 14
Venous
blood mass-balance equation, 262
-equilibration model of organ
elimination, 83-86
Vessel-poor group (VPG) of organs,
447
Vessel-rich group (VRG) of organs,
447
Vial equilibration, 164
Vinyl chloride monomer (VCM),
456-458
Virtual steady states, 98-99
validity of assumption of, 105-106
Virtually safe doses (VSD), 296-298
Volume of distribution, 31
VPG (vessel-poor group) of organs,
447
VRG (vessel-rich group) of organs,
447
VSD (virtually safe doses), 296-298
W
Well-stirred model of organ
elimination, 83-86, 113
Representative terms from entire chapter:
physiologically based
