Page 58 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Concepts in Veterinary Toxicology Chapter | 1 25

VetBooks.ir the air, whether it is a diluted gas or airborne particulate test agent inhaled can be estimated from knowledge of
The situation is much more complex for a test agent in
the air volume inspired and the concentration of the test
material. In both cases, it will be necessary to sample and
agent in the air. In many studies the air concentration of
measure the concentration of the test agent in the air at a the test agent may be used as a surrogate measure of
location as close as possible to the breathing zone of the exposure. As indicated earlier, exposure and dose are not
experimental subjects. For both particulate material and synonymous. However, in many studies it may be neces-
reactive gases, there may be substantial loss of the test sary to use the concentration of the test agent in the feed,
agent in the delivery system between the generator used water or air as a surrogate measure of dose.
to create the test atmosphere and the breathing zone of
the subject(s). Care needs to be taken to minimize such
losses. For a toxic agent in a particulate matter form, it is Describing Absorption, Distribution,
essential to know not only the concentration of the test Metabolism, and Excretion
agent, but the size distribution of the particulate matter
since the aerodynamic particle size distribution will influ- A number of different parameters may be evaluated in
ence the fraction of the inhaled material that will be assessing the kinetics of a test agent (recall Fig. 1.7).
deposited and where it deposits in the respiratory tract. In Some of the common parameters and terms used are
some experiments, it may be possible to use a plethysmo- shown in Table 1.2. The four key events involved are
graph to measure respiration of individual subjects during absorption, distribution, metabolism, and excretion. It is
inhalation exposure. This is most readily accomplished important to recognize that species differences may exist
when the exposure period is relatively brief as in a study for each of these events. Absorption is the amount of the
of the toxicokinetics of the agent. The total quantity of material that enters the body. As already discussed, the

TABLE 1.2 Common Terms Used to Describe the ADME Characteristics of Chemicals
Term Abbreviation Definition
Concentration C p Concentration of a chemical in plasma (p) at a specific time (t)
Time t Chronological measurement of a biological function
Half-life t 1/2 Time required for exactly 50% of a drug to undergo some defined function (i.e., absorbed,
distributed, metabolized, or excreted)
Volume of distribution V d Unitless proportionality constant that relates plasma concentration of a chemical to the
total amount of that chemical in the body at any time after some pseudo equilibrium has
been attained
Volume of distribution V d(ss) Same as V, except measured when the chemical has reached a steady state in the body
(steady state)
Area under the curve AUC Total area under the plasma chemical concentration curve from t 5 0to t 5 N after the
animal receives one dose of the chemical
Body clearance of a Cl B The sum of all types of clearance from the body
chemical
Renal clearance of a Cl R Volume of chemical that is completely cleared by the kidneys per unit of time (ml/min/kg)
chemical
Nonrenal clearance of Cl NR Volume of chemical that is completely cleared by organs other than the kidneys per unit
a chemical of time (ml/min/kg)
Dose D The amount of chemical that is administered to an animal; can be further defined as the
total dose, that total dose the animal was exposed to, or the absorbed (effective) dose, that
being the fraction of the total dose that was actually absorbed by the animal
Bioavailability F Also known as systemic availability of a chemical. The quantity of percentage portion of
the total chemical that was absorbed and available to be processed (CME) by the animal,
in the case of intravenous administration, F 5 100%
ADME: absorption, distribution, metabolism and excretion; CME: chemical metabolism and excretion.
Adapted from Spoo, W. (2004). Toxicokinetics. In: Plumlee, K.H. (Ed.), Clinical Veterinary Toxicology. Elsevier, pp. 8 12 (Spoo, 2004).