Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 132

k a k e

10

Volume =
Vd

Dose

y-intercept = k a FDose/Vd(k a -k e )

1

slope = -k e /2.303

0.1

slope = -k a /2.303

0.01

0 6 12

Time (h)

18

Figure 6.6 Estimation of volume of distribution and absorption and elimination rate constants for
the one-compartment model in Figure 6.5 by graphical methods (i.e., curve stripping). Data are
shown in Table 6.1.

Table 6.1 Data Used for the Method of Residuals Example Shown in Figure 6.6

Extrapolated concentration
(mg/L plasma) Time (h) Plasma Residual

0.25 0.218 1.083 0.865

0.5 0.382 1.057 0.675

1 0.597 1.005 0.408

2 0.759 0.910 0.151

4 0.724

8 0.499

12 0.334

16 0.224

20 0.150

24 0.101

Storage with Repeated Exposures
Repeated exposure to a chemical at constant time intervals may lead to accumulation
of the chemical in the body until a steady state is achieved. During any exposure inter-
val τ at steady state, the rate of chemical entry into the body is equal to the rate of its
elimination (i.e., amount absorbed equals amount eliminated). Wagner (1967) proposed
the concept of a concentration index ( R C ), which provides information with regard to
the increased accumulation over multiple exposures. R C is defined as the ratio of the