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Questions and Answers
What does a two-compartment model have in terms of characteristic half-lives?
What does a two-compartment model have in terms of characteristic half-lives?
Why might the elimination of a highly lipid-soluble substance from blood be rapid at first?
Why might the elimination of a highly lipid-soluble substance from blood be rapid at first?
In a plot of loge(concentration in blood) against time in a two-compartment model, what does the appearance of two straight line regions indicate?
In a plot of loge(concentration in blood) against time in a two-compartment model, what does the appearance of two straight line regions indicate?
How are the two half-lives determined in a two-compartment model?
How are the two half-lives determined in a two-compartment model?
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What determines the kinetics of a toxic substance in a two-compartment model when the concentration in blood falls?
What determines the kinetics of a toxic substance in a two-compartment model when the concentration in blood falls?
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How is the initial concentration estimated in each compartment in a two-compartment model?
How is the initial concentration estimated in each compartment in a two-compartment model?
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What type of relationship is observed when plotting loge(concentration) against time in toxicokinetics?
What type of relationship is observed when plotting loge(concentration) against time in toxicokinetics?
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Why are more detailed models like multiple compartment models necessary in toxicokinetics?
Why are more detailed models like multiple compartment models necessary in toxicokinetics?
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Which compartments are involved in the toxicokinetic model depicted in Figure 3.9?
Which compartments are involved in the toxicokinetic model depicted in Figure 3.9?
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When can partition coefficients be used in toxicokinetic models?
When can partition coefficients be used in toxicokinetic models?
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In which scenario must the metabolic pathways and reaction kinetics be known in toxicokinetic modeling?
In which scenario must the metabolic pathways and reaction kinetics be known in toxicokinetic modeling?
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What does the two straight line regions observed in a plot of loge(concentration) against time indicate?
What does the two straight line regions observed in a plot of loge(concentration) against time indicate?
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What is the characteristic feature of substances exhibiting first order toxicokinetics?
What is the characteristic feature of substances exhibiting first order toxicokinetics?
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In a first-order kinetic process, how much of the initial concentration remains after 3 half-lives?
In a first-order kinetic process, how much of the initial concentration remains after 3 half-lives?
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Which type of kinetics is characterized by the concentration in tissues changing steadily with time?
Which type of kinetics is characterized by the concentration in tissues changing steadily with time?
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What does the graph of the logarithm of concentration against time look like for substances with first-order kinetics?
What does the graph of the logarithm of concentration against time look like for substances with first-order kinetics?
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What is another term for linear kinetics in toxicokinetics?
What is another term for linear kinetics in toxicokinetics?
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In toxicokinetics, which substances have elimination rates proportional to their concentration in the body?
In toxicokinetics, which substances have elimination rates proportional to their concentration in the body?
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Study Notes
Toxicokinetics
- Toxicokinetics refers to the study of the rates of uptake and excretion of toxic substances in the body.
- Pharmacokinetics and toxicokinetics are essentially the same.
First Order Kinetics
- Most substances are eliminated at a rate proportional to their concentration in the body.
- The higher the concentration, the more rapid the elimination.
- Substances with first order kinetics have a characteristic half-life (t1/2).
- The initial concentration in the body falls to one half in 1 half-life, to 1/4 after 2 half-lives, 1/8 after 3 half-lives, and 1/16 after 4 half-lives.
Graph of Concentration vs. Time
- A graph of the logarithm of concentration of a substance in the body against time will be a straight line if the substance has first order single compartment kinetics.
- A two-compartment model may show two straight line regions, corresponding to the two phases of elimination.
Two-Compartment Model
- The two-compartment model involves the major body compartments, including the lungs, dermis, muscles, adipose tissue, white marrow, and liver.
- The model considers the rates of transport between compartments according to their capacities and blood perfusion rates.
- The model can be used if partition coefficients are known, but in other cases, metabolic pathways and reaction kinetics must also be known.
Elimination Curve
- The elimination curve for a toxic substance with two-compartment first order kinetics is a curve that asymptotically approaches zero.
- The perfusion for each compartment (in litres per minute) is an important factor in the model.
Half-Lives
- A two-compartment model has two characteristic half-lives, one for each compartment.
- The half-lives can be calculated from the slopes of the two straight line regions and extrapolated to estimate the initial concentration in each compartment.
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Description
Explore the concept of fluid dynamics analogies in pharmacokinetics through a scenario involving tanks with different flow rates. Understand how the concept applies to the elimination of lipid-soluble substances from blood and fat stores.
