Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 125

In Eqs. (7) and (8), C T is the observed concentration at the last time point T, and
β is the slope of the terminal elimination phase of the log plasma concentration vs.
time curve. The mean residence time (MRT) represents the overall persistence of the
chemical in the body, and is thus the average time that the species stays in the body. It
also represents the time required for 63.2% of the chemical to be eliminated from the
body and can be calculated as:

AUMC
AUC

MRT = . (9)

The bioavailability ( F ), which is the fraction of chemical that is absorbed after extra-
vascular administration, may also be calculated using noncompartmental models. Because
the process of absorption is bypassed with intravenous administration, the bioavailability
after intravenous administration is assumed to be unity. It is determined for extravascular
administration (e.g., oral, dermal) with reference to an intravenous dose as:

D
D

AUC
AUC

iv ex

F = , (10)

ex iv

where D iv and D ex are the intravenous and extravascular doses, and AUC iv and AUC ex
are the areas under the plasma concentration vs. time curve after intravenous and
extravascular doses. When the intravenous and extravascular doses are the same, F is
simply the proportion of AUC after extravascular and intravenous doses. Bioavailability
is often referred to as a percentage. For example, the bioavailability of orally adminis-
tered permethrin is 0.61, or 61% ( Anadon et al., 1991 ). A number of factors, including
the route of administration and species, may affect it. For example, the bioavailability
of paraquat was 45, 12, or 3.8% after intratracheal, oral, or dermal doses, respectively
( Chui et al., 1988 ). Species-dependent bioavailability has been shown for orally admin-
istered metosulam, which was only 20% in mice and dogs, but greater than 70% in rats
( Timchalk et al., 1996 ).
Plasma clearance (Cl), a measure of the inherent ability to remove a chemical from
the body, is the volume of plasma that is cleared of the chemical per unit time. Cl after
an intravenous dose is calculated as:

D

iv

Cl = . (11)

AUC

Cl can be calculated after an extravascular dose only if the bioavailability is 100%
(i.e., F  1).
The apparent volume of distribution at steady state ( V ss can be calculated after a
single iv dose) is:

= Cl MRT × . (12)

V ss

iv