Page 123 - The Toxicology of Fishes

Toxicokinetics in Fishes 103

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PARAOXON CONCENTRATION IN PLASMA (µg/mL)

1

0.1

0.01

0.001

0 1 2 3 4 5 6
HOURS
FIGURE 3.21 Paraoxon plasma concentration–time profile in rainbow trout after intraarterial injection. Symbols represent
the experimentally determined concentrations, and the line represents the least-squares fit of a two-compartment-model-
based biexponential equation. (Adapted from Abbas, R. et al., Toxicol. Appl. Pharmacol., 136, 194–199, 1996.)

early and often rapid decline in plasma concentration is thought to be due primarily to a redistribution
of the injected compound, while the later elimination or β phase is controlled by rate limitations on
chemical elimination. A two-compartment model for intravascular administration of a bolus dose is
described in the following section. Space does not permit the presentation of other multiple-compartment
models; however, the principles illustrated by this relatively simple model apply generally to more
complex models.
Intravascular Bolus Administration
This widely used model represents the body as two compartments (Figure 3.20B). Toxicant enters the
central compartment, distributing instantaneously. Some of this toxicant moves from the central com-
partment into a peripheral compartment. Once it is in the peripheral compartment, the toxicant is again
assumed to distribute instantaneously. The central compartment generally represents the blood and highly
perfused tissues such as the liver, kidney, and GIT. The peripheral compartment usually represents poorly
perfused tissues, including muscle and fat. The brain may be associated with either compartment,
depending on whether the blood–brain barrier limits the rate of toxicant exchange between the blood
and brain tissues.
Following the intravascular administration of a bolus dose (X ), mass-balance equations that describe
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the rate of change of the amount of toxicant in compartments one and two may be written as follows:
dX /dt = k X – k X – k X 1 (3.61)
21
2
12
10
1
1
dX /dt = k X – k X 2 (3.62)
21
1
2
12
where X and X are the amounts of toxicant in compartments 1 and 2, k and k are first-order
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21
1
2
intercompartmental transfer rate constants, and k is a first-order rate constant for chemical elimination
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