Glossary
Notation (Cp)¥ [also (Cp)ss] concentration of drug in
A coefficient in the equation for plasma drug
concentration over time for a two-compart-
ment intravenous bolus model
AUC area under the plasma drug concentra-
tion versus time curve
(AUC) ¥
0 the area under the plasma concentra-
tion time versus curve from t ¼ 0 to time t ¼ ¥
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ARE amount of drug remaining to be elimi-
nated at time t
AUMC (area under the [first] moment
curve) a synonym for the first statistical
R¥
moment: 0 tf ðtÞdt: It is estimated by the
trapezoidal approximation of the area under
the curve having the product of plasma drug
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concentration multiplied by time on the
ordinate and time on the abscissa. The ratio
AUC/AUMC is equal to MRT.
B coefficient in the equation for plasma drug
concentration over time for a two-compart-
ment intravenous bolus model; it is the y-axis
intercept of the terminal log linear segment
of the plasma drug concentration versus time
curve
Cl or Cls systemic clearance of a drug
ClH hepatic clearance of a drug
Clint intrinsic clearance of a drug
0
Cl int intrinsic free (unbound) clearance of a
drug
ClNR non-renal clearance of a drug
ClR renal clearance of a drug
Cp plasma drug concentration at time t fol-
lowing drug administration
(Cp)0 plasma drug concentration at t ¼ 0
(immediately) following drug adminis-
tration)
(Cp)max peak plasma concentration after a
single oral dose of drug
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the plasma at steady state
(Cp ) ss average steady-state plasma drug
concentration
(Cp¥)max [also (Cpss)max] peak steady-state
plasma drug concentration
(Cp¥)min [also (Cpss)min] minimum or
trough, steady-state plasma drug
concentration
(Cpn)t plasma drug concentration at a time t
after the administration of the nth dose of a
multiple dosing regimen
(Cp)t0 plasma drug concentration at a time t0
after the cessation of an intravenous infusion
(Cp)HI for multiple intravenous infusion, a
‘‘peak’’ concentration that is collected late
and that requires mathematical adjustment
to estimate the ‘‘peak’’ concentration that
would have been recorded if the blood sam-
ple had been collected on time
(Cp)LO for multiple intravenous infusion, a
trough concentration that is collected early
and that requires mathematical adjustment
to estimate the trough concentration that
would have been recorded if the blood sam-
ple had been collected on time
(Cp)‘‘PK’’ the useable peak concentration for a
two-compartment drug administered by
multiple intravenous infusion; this occurs
when a semilogarithmic plot of plasma drug
concentration versus time becomes linear
(for vancomycin: approximately 1–2 h after
the infusion is stopped)
dX/dt instantaneous rate of change in the
mass of drug present in the body (exclusive
of the gastrointestinal tract) at time t (if dX/dt
is positive, mass is increasing over time; if it is
negative, mass is decreasing over time)
dXe/dt the rate of drug elimination; the rate
of loss of drug from the body as a whole; it is
377
 378 G lo s sa r y
equal to (þ)KX for one-compartment drugs
(both intravenous bolus and oral) and is
equal to (þ)k10XC for two-compartment
drugs (both intravenous bolus and oral);
moreover, it is equal to
(dX/dt) for intrave-
nous bolus, but not for oral, dosing
dXu/dt the rate of change of drug eliminated
by the body by urinary excretion
des subscript indicating a desired, or target,
plasma drug concentration
DL loading dose of drug
(DL)inf administered dose of a loading intra-
venous infusion
(DL)IV loading dose administered as an intra-
venous bolus injection
E the hepatic extraction ratiofora drug;itisthe
fraction drug metabolized (and eliminated) by
the liver during a single pass through the liver
f fraction of an oral dose absorbed from the
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gastrointestinal tract into the portal (not the
systemic) circulation; affected predomi-
nately by dissolution of drug in the gastroin-
testinal tract
f [in context] fraction drug remaining in the
body at time t after an intravenous bolus dose
of drug
F the fraction of an extravascularly adminis-
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tered dose of drug that is absorbed into the
systemic circulation; it is the extent of a
drug’s bioavailability
fC fraction of total drug in the body that is
present in the central compartment at time t
fC* fraction of total drug in the body that is
present in the central compartment in the
post-distribution phase
FG extent of systemic absorption for a generic
formulation of drug
FIV fraction of an intravenous dose reaching
the general circulation; by definition, this
equals 1.0
FPO [or Foral] fraction of an oral dose reach-
ing the general circulation; it is the product:
f  F*
FS extent of systemic absorption for a stan-
dard (trade name) formulation of drug
fss for multiple dosing, the ratio of plasma
drug concentration at time t to plasma drug
concentration that would be achieved at
steady-state; fraction of steady state achieved
at time t
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fup fraction drug unbound in the plasma
fut fraction drug unbound in the tissue
F* fraction of drug in the portal circulation
that goes on to survive the first-pass effect
and enter the systemic circulation; it equals
1
E, where E is the hepatic extraction ratio
for the drug
I coefficient in the equation for plasma drug
concentration over time for a one-compart-
ment extravascular model; it is the intercept
on the y-axis of the extrapolated terminal
linear segment of a semilogarithmic plot of
plasma drug concentration (Cp) versus time
after an oral dose of drug
K (or Kel) the first-order elimination rate
constant for a one-compartment drug
Ka the first-order absorption rate constant
Ke the first-order rate constant for renal
excretion of drug
Km the first-order rate constant for metabo-
lism of drug; or [in context] the Michaelis
constant in non-linear pharmacokinetics
K0 the zero-order elimination rate constant
Kother the first-order rate constant for elimi-
nation of drug by a process other than metab-
olism or renal excretion
K10 for a two-compartment drug, the first-
order rate constant for elimination of drug
from the central compartment
K12 for a two-compartment drug, the first-
order rate constant for transfer from the cen-
tral to the peripheral compartment
K21 for a two-compartment drug, the first-
order rate constant for transfer from the
peripheral to the central compartment
MAT mean absorption time; mean residence
time in the gastrointestinal tract; synony-
mous with MRTGIT
MDT mean dissolution time in vivo of a solid
oral dosage form administered to a human
subject
MRT mean residence time; the mean (aver-
age) time for a mass of intact drug molecules
to transit through the body; it is a composite
of all disposition processes and, when appli-
cable, drug release from the dosage form and
absorption
n the dose number (e.g. the fifth dose for n ¼ 5)
NaPH abbreviation used for sodium
phenytoin

PH abbreviation used for phenytoin (free
acid)
Q intravenous infusion rate rate (mass/time
units)
QH hepatic plasma flow
QL the infusion rate of a loading intravenous
infusion
r the Dost ratio
R accumulation factor; [in context] the rate
of administration of drug
S the salt form correction factor
t time; [in context] time since the latest dose
in a series of multiple doses was administered
t0 time following the cessation of an infusion
T time at which the infusion is stopped
tinf the duration of an intravenous infusion
(time during which the intravenous infusion
is being infused into the patient)
t0 lagtime (time elapsed after oral dosing
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until Cp begins to rise above zero
tp time of peak plasma drug concentration
after a single oral dose
0
t p time of peak plasma drug concentration
after multiple oral doses to steady state
t1/2 first-order elimination half life
V apparent volume of distribution
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Vb (Vdb) for a two-compartment model drug,
the apparent total volume of distribution in
the post-distribution phase after a single dose
of drug
VC apparent volume of distribution of the
central compartment for a two-compartment
drug
Vcirc actual circulatory volume
Vmax maximal velocity (rate) of elimination
in non-linear (Michaelis–Menten) kinetics
Vss (Vdss) for a two-compartment model
drug, the apparent total volume of distribu-
tion at steady state
VTBW volume of total body water
X the mass, or amount, of drug present in the
body at time t; this does not include any drug
that may be present in the gastrointestinal
tract
Xa the mass, or amount, of drug capable of
being absorbed present in the absorption site
(e.g. the gastrointestinal tract) at time t
(Xa)t¼0 the mass, or amount, of absorbable
drug present in the absorption site (e.g. the
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Glossary 379
gastrointestinal tract) at time t ¼ 0; this is
equal to FX0
Xbag for statistical moment analysis, the
mass of drug remaining in the intravenous
infusion bag at time t
XC for a two-compartment model drug, the
mass of drug present in the central compart-
ment at time t
(XC)0 for a two-compartment model drug,
the mass of drug present in the central com-
partment at time t ¼ 0
XGIT mass of drug in the gastrointestinal tract
at time t
(XGIT)0 mass of drug in the gastrointestinal
tract at t ¼ 0
X0 the dose of drug administered
(Xinf)0 administered dose of a multiple inter-
mittent intravenous infusion
(Xm)t mass of metabolite present in the
blood at time t
(Xmu)t mass of metabolite present in the
urine at time t
Xperi for a two-compartment drug, the mass
of drug present in the peripheral compart-
ment at time t
Xt¼0 mass of drug present in the body at t ¼ 0
(immediately) following drug adminis-
tration)
(Xu)cum cumulative mass of drug excreted in
the urine at time t
( X u )¥cum cumulative mass of drug excreted
in the urine at time ¼ ¥
X* for a two-compartment model drug, the
mass of drug present in the body in the
post-distribution phase
a the fast disposition rate constant for a two-
compartment drug (usually representing the
rate of drug distribution)
b the slow disposition rate constant for a two-
compartment drug; it is derived from the
slope of the terminal linear segment of Cp
versus time and, in this phase, is usually
indicative of elimination of drug from the
body as a whole
l general term for a rate constant, e.g. K, Ka, b,
etc.
t fixed dosing interval for a multiple inter-
mittent dose regimen
F fluctuation factor at steady state
 380 G lo s sa r y

Definitions may then undergo elimination via the first-

pass effect
circulation, systemic blood vessels that
active transport a type of specialized trans-
distribute absorbed drug throughout the
port where energy is used to move a drug
body; intravenously administered drug goes
molecule against a concentration gradient
directly into the systemic circulation
ADME acronym for the pharmacokinetic clearance a pharmacokinetic parameter
processes absorption, distribution, metabo- that indicates the volume of plasma from
lism, and excretion
which all drug is removed (cleared) per unit
absorption the process by which an extra-
time
vascularly administered drug gets into the
compartment a virtual space into which
systemic circulation
absorbed drug can be considered to be dis-
adsorption binding on to a surface
tributed; some drugs remain in a central com-
AUC (area under the [plasma drug con-
partment comprising the vasculature and the
centration versus time] curve) an indi-
well-perfused organs and tissues, while other
cator of extent of absorption of an orally
drugs undergo a further transfer into a more
administered drug formulation
peripheral space termed the tissue
binding, plasma protein drug binding to
compartment
albumin and other proteins in the blood; conjugate acid the substance produced
since bound drug is inactive, displacement
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when a weak base gains a proton

of drugs from binding sites by other drugs
deaggregation a process by which granules
may be important, especially for drugs with
from the disintegration of tablets or capsules
a high degree (>90%) of binding
are further decreased in size to fine particles
bioavailability, extent the fraction (F) of
diffusion movement of drug molecules
orally administered drug that reaches (is
that is powered by a concentration gradi-
absorbed into) the systemic circulation; it is
ent; (see passive diffusion and facilitated
also called absolute bioavailability
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diffusion]
bioavailability, rate the rate of absorption
disintegration a process by which a tablet
of an orally administered drug
or capsule is broken down into particles
bioavailability, relative the extent of called granules
orally administered drug reaching the sys- dissociation in solution, the physical sepa-
temic circulation compared with that of
ration of anions and cations of an acid, a base
another extravascular formulation
or a salt; dissociation approaches 100% for
bioequivalence study a study that com-
most salts and for strong acids and bases,
pares the relative rate and extent of bioavail-
while the degree of dissociation of weak acids
ability (systemic absorption) of a generic
and bases is governed by their dissociation
drug with the rate and extent of bioavailabil-
constants
ity of the standard formulation of the same
dissolution the process by which a drug
drug; it is the basis of approval of a generic
goes into solution in which individual drug
formulation by the US Food and Drug
molecules are separated by molecules of sol-
Administration (FDA) vent (water)
bioequivalent a formulation deemed by distribution the process in which a drug
the FDA to have essentially the same rate
molecule is carried by the circulation to
and extent of absorption as the standard
well-perfused organs and tissues and,
(see also therapeutic equivalent)
depending on the drug, even more exten-
circulation, portal blood vessels draining
sively to distant tissues
the gastrointestinal tract; orally adminis-
effect response of the body to a pharmaco-
tered drug traversing the gastrointestinal
logical agent; this response may be either
tract membrane goes into the portal circula-
therapeutic or toxic; it is characterized by
tion, which conveys it to the liver, where it
an onset, intensity, and duration

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elimination removal of active drug from
the body by metabolism and/or excretion
processes
elimination half life for a drug with linear
elimination pharmacokinetics, the time it
takes for 50% of drug present to be eliminated;
it is constant for a given patient receiving a
particular drug
elimination pharmacokinetics, linear
elimination following a first-order process; in
this situation, AUC is a linear function of
dose
elimination pharmacokinetics, non-
linear elimination following a process
other than a first-order process; in this situa-
tion, AUC is not a linear function of dose;
large changes in steady-state plasma drug
concentrations can occur for relatively small
changes in dose
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excretion physical removal of a drug mole-
cule or a metabolite from the body; excretion
is predominantly by the kidney (renal excre-
tion) and in the bile (biliary excretion)
excipient ingredients in a pharmaceutical
formulation, other than the active ingredi-
ent, which confer useful properties to the for-
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mulation (e.g. disintegrants, lubricants,
stabilizing agents)
extraction ratio the fraction of drug elim-
inated from the body during a single pass
through an organ of elimination (e.g. the
liver)
facilitated diffusion diffusion of a drug
molecule across a membrane aided by a car-
rier molecule
Fick’s first law law that governs the rate of
diffusion across a membrane
first-order process a process whose rate is
directly proportional to the current amount
of the compound being transferred by the
process; linear elimination pharmacokinetic
is an example of a first-order process
first pass effect the situation whereby the
fraction of a dose of orally administered drug
that reaches the systemic circulation is equal
to 1 minus its hepatic extraction ratio
formulation a dosage form of a particular
drug
generic a formulation of drug prepared by a
company that did not innovate the drug; the
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Glossary 381
company will present bioequivalency data to
the FDA for its approval, with a view to mar-
keting the generic formulation when the
innovator drug formulation comes off patent
hydrophilic ‘‘water-loving,’’ possessing a
low octanol/water partition coefficient
ionization charge separation in a mole-
cules, producing electron-depleted cations
and electron-rich anions; salts can be fully
ionized in the dry state
kinetics rate
lipid bilayer biological membrane
lipophilic ‘‘fat-loving;’’ possessing a high
octanol/water partition coefficient
metabolism effective removal of a parent
drug molecule by converting it to a chemi-
cally different species; usually this results in
an inactive molecule that is more readily
excreted than the parent; phase I and phase
II metabolism pathways exist
micronization reduction of a drug’s parti-
cle size to the mm range; necessary for rapid
dissolution of some drugs
minimum effective concentration
(MEC) the plasma drug concentration
below which, on the average, no therapeutic
effect occurs
minimum toxic concentration (MTC)
the plasma drug concentration above which,
on the average, toxicity occurs
nephron the functional unit of the kidney,
comprising glomerulus, tubules and sur-
rounding vasculature
Noyes–Whitney equation equation that
governs the rate of dissolution of particles of
drug
octanol/water partition coefficient the
amount of drug that goes into the octanol phase
compared with the amount of drug that goes
into the aqueous phase in a two-phase system;
having a larger value for more lipophilic drugs
parameter a pharmacokinetic constant for
a given patient receiving a particular drug
parenteral by injection
passive diffusion movement of drug mole-
cules that is powered by a concentration gra-
dient; diffusion occurs across the lipid bilayer
(membrane) for lipophilic drugs and via
aqueous channels (pores) for small hydro-
philic drugs