18 Questions
What does a two-compartment model have in terms of characteristic half-lives?
Two half-lives, one for each compartment
Why might the elimination of a highly lipid-soluble substance from blood be rapid at first?
Due to high initial concentration in blood
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?
Two different phases of elimination
How are the two half-lives determined in a two-compartment model?
By calculating slopes of the two straight line regions
What determines the kinetics of a toxic substance in a two-compartment model when the concentration in blood falls?
Rate of release from fat stores to blood
How is the initial concentration estimated in each compartment in a two-compartment model?
By extrapolating lines back to zero time
What type of relationship is observed when plotting loge(concentration) against time in toxicokinetics?
Two straight line regions
Why are more detailed models like multiple compartment models necessary in toxicokinetics?
To consider the rates of transport between organs and tissues with different characteristics
Which compartments are involved in the toxicokinetic model depicted in Figure 3.9?
Lung, Dermis, Muscle, Adipose tissue
When can partition coefficients be used in toxicokinetic models?
For non-metabolized substances if partition coefficients are known
In which scenario must the metabolic pathways and reaction kinetics be known in toxicokinetic modeling?
Only for metabolized substances
What does the two straight line regions observed in a plot of loge(concentration) against time indicate?
First-order kinetics
What is the characteristic feature of substances exhibiting first order toxicokinetics?
The concentration in the body falls to half in each half-life
In a first-order kinetic process, how much of the initial concentration remains after 3 half-lives?
1/8
Which type of kinetics is characterized by the concentration in tissues changing steadily with time?
Linear kinetics
What does the graph of the logarithm of concentration against time look like for substances with first-order kinetics?
A straight line
What is another term for linear kinetics in toxicokinetics?
'Zero order kinetics'
In toxicokinetics, which substances have elimination rates proportional to their concentration in the body?
'First order kinetics' substances
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.
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.
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