Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 135

Hence,

1 44 . FDt

FD

1 44 . t

1 2 / 1 2 /

.

R =

(49)

=

A

τ

τ

Multicompartment Models
Many chemicals do not rapidly equilibrate between blood and tissues, and their plasma
concentration-time profiles do not conform to the one-compartment model already
described. Instead, elimination from plasma is multiphasic, the simplest case being biphasic
elimination. The early phase is referred to as the distribution phase, and the later phase
is the postdistribution or elimination phase. The plasma concentration of the chemical
declines more rapidly during the distribution phase than in the elimination phase. Two
schematics of two-compartment models are shown in Figure 6.3 . The central compart-
ment includes blood and tissues in which the chemical rapidly equilibrates (e.g., tissues
that receive a high blood flow) and is considered a homogeneous compartment. This
is analogous to the single compartment of a one-compartment model. The peripheral
compartment consists of tissues for which equilibrium is not instantaneous. In classical
compartmental models, the chemical moves between the central and the peripheral com-
partments with associated transfer rate constants, but elimination is assumed to occur only
from the central compartment with an associated elimination rate constant ( Figure 6.8 ).
Absorption, distribution, and elimination are assumed to be first-order processes.

Figure 6.8 Representation of a two-compartment model with iv administration and first-order elimi-
nation, including a typical plasma concentration vs. time profile (linear and logarithmic scales).