Biology Reference
In-Depth Information
Figure 6.10 Representation of a two-compartment model with first-order absorption (i.e., extravas-
cular administration) and first-order elimination, including a typical plasma concentration vs time
profile (linear and logarithmic scales).
Physiologically Based Models
Unlike classical compartmental models, physiologically based pharmacokinetic (PBPK)
models represent physiological and anatomical reality ( Figure 6.11 ). The compart-
ments are connected by blood flow, and chemicals may enter the body by any route.
The model in Figure 6.11 incorporates exposure by the oral, dermal, and inhalation
routes and elimination by urinary excretion, exhalation, and metabolism. PBPK mod-
els use mathematical descriptions of chemical disposition that are based on the physi-
ological, physicochemical, and biochemical determinants of disposition, which include
biochemical reaction rates and tissue partition coefficients for the chemistry and physi-
ology (e.g., organ volumes, blood flows, respiration rates) of the animal. PBPK models
do not assume that all processes governing disposition are linear, and saturable metabo-
lism (Michaelis-Menten kinetics), for example, can be easily incorporated into them.
PBPK models exist for pesticides from a variety of chemical classes ( Table 6.3 ).
Like classical compartmental models, the compartments in Figure 6.11 represent
organs or tissue groups in which a chemical is uniformly distributed, and arrows rep-
resent the pathways that govern chemical disposition. Each compartment has an asso-
ciated volume. Absorption is represented by arrows to the portals of entry for various
routes of exposure, blood flow is represented by arrows that interconnect the compart-
ments of the model, and metabolism and excretion are represented by arrows from
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