Page 171 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

138 SECTION | I General

VetBooks.ir IH Arterial Vascular space Free drug Venous
blood
blood
Alveolar space Ex Extracellular space
Lung
Intracellular space
Tissue Free drug
Brain
binding sites

Fat

Elimination Biotransformation
Muscle
IM FIGURE 8.5 Schematic diagram of a generic tissue block physiologi-
cally based pharmacokinetic model, with subcompartments as well as
Ex possible binding sites and sources of elimination.
Kidney Venous blood

Bone Adipose
PO
Arterial blood
GI tract Ex Muscle
Liver
Kidney
Rapid
tissues Plasma
Renal clearance
Slow Carcass IV dose
tissues

Skin
Liver
PO dose
Deacetylation Acetylation
SQ TD IV
Liver
metabolite
FIGURE 8.4 Schematic diagram of a generic whole body physiologi-
cally based pharmacokinetic model. metabolite Plasma
Body
metabolite
low blood flow tissues. The compartments can be subdi-
vided into extracellular and intracellular spaces (Colburn,
Clearance metabolite
1988). Tissue blocks and their subcompartments can be
combined to make the model as simple or as complex as
FIGURE 8.6 Schematic diagram of a physiologically based pharmacoki-
needed. A schematic diagram for a generic whole body
netic model, used in the prediction of sulfamethazine tissue residues in
model is shown in Fig. 8.4. Fig. 8.5 depicts a generic tis- swine.
sue block with subcompartments as well as possible bind-
ing sites and sources of elimination. In contrast to the full tissues were specifically included in the model. The rest
body model, Fig. 8.6 presents a schematic diagram used of the body was lumped into a single tissue block.
in the prediction of sulfamethazine (SMZ) tissue residues Elimination occurs by renal filtration and is schematically
in swine (Buur et al., 2005). This model contains several represented using arrows that are not directed into the
simplifications, including a reduced number of tissue plasma compartment. The main metabolite is also mod-
blocks, and the combination of tissue blocks into a single eled, and the two xenobiotics are linked together via the
compartment. Because the model was designed to predict liver tissue block. This is an example of how model com-
SMZ residues in edible swine tissues, only the edible plexity can be optimized to achieve specific aims.