Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 126

The first-order elimination rate constant ( k e ) and elimination half-life ( t 1/2 ) can also
be calculated after a single iv dose for chemicals that appear to be characterized by a
one-compartment model (see One-Compartment Model), from the relationships:

1
iv = k e

MRT (13)

and:

= 0 . 693MRT . (14) t 1 2

/ iv

For chemicals that cannot be described by a one-compartment model,

1
k

MRT iv = , (15)

′

e

Cl
V

′ =

k , (16)

e

ss

and the effective elimination half-life is the product of 0.693 and MRT iv .

Overview of Classical Compartmental Models
Classical compartmental models typically divide the body into one or more com-
partments that have no physiological or anatomical reality ( Figure 6.3 ). It is assumed
that the rate of transfer between compartments and the rate of elimination from the
compartments are linear or first-order processes. Each model has an associated series
of mathematical equations that describe the absorption, elimination, and transfer of
chemicals between compartments. These equations are dependent only on the model
structure and are independent of the chemical under study. Classical compartmental
models can provide important parameters that describe chemical disposition, including
the volume of distribution, absorption and elimination rate constants, elimination half-
life, and plasma clearance. In the following discussion, elimination is assumed to occur
only from compartment one, which is referred to as the central compartment.

One-Compartment Model
A one-compartment model ( Figure 6.4 ), which represents the body as a single homo-
geneous compartment, adequately describes the pharmacokinetics of chemicals that
rapidly equilibrate between blood and tissues. Therefore, it is reasonable to assume that
the concentration of the chemical in blood (or plasma) is proportional to its concen-
tration at the site of toxicity.