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WHAT IS TOXICOKINETICS?
• One-compartment
• Two-compartment
• Multiple compartment
e.g. blood is a compartment
other compartments: adipose tissue, liver, kidney
ONE-COMPARTMENT MODEL
• Disadvantages are
– More information is needed
– Mathematics is difficult
– Values for parameters are often poorly defined
PHYSIOLOGIC TOXICOKINETICS
• Physiologic model
(laboratory animals)
– Simulation
– Basic unit is the
Lumped
Compartment
Toxicant leaves the vascular space at a certain venous concentration:
Cout = concentration of toxicant in the vascular space
PHYSIOLOGIC TOXICOKINETICS PARAMETERS
• Anatomical
– Used to physically describe the various compartments
– Size (volume)
• Physiologic
– Blood flow (blood flow rate Qt ml/min)
– Cardiac output or total blood flow rate(Qc)
– Alveolar ventilation rate (Qp)
– Renal or hepatic
PHYSIOLOGIC TOXICOKINETICS PARAMETERS
• Thermodynamic
Total concentration of xenobiotic in tissue = conc. of free xenobiotic in that tissue
(Ct) = (Cf)
Assumptions:
1. Total and free concentrations are at equilibrium
2. Only free xenobiotic can be exchanged between the tissue
subcompartments
PHYSIOLOGIC TOXICOKINETICS PARAMETERS
• Transport
– Passive diffusion (Fick’s Law)
• First order process
– Thin membrane, large surface areas, large
concentration differences ; enhance diffusion
– Membrane trasnporters
PHYSIOLOGIC TOXICOKINETICS PARAMETERS
• Lung
– Inhalation is a common route of exposure
• Liver
– Major organ for biotransformation of xenobiotics
• Blood
– Tissue compartment is linked by the circulatory
system
THANK YOU