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Case 10 Pharmokinetics & dynamics
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Case van 11 pagina's voor het vak BGZ2004 Food for Life aan de UM
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BGZ2004Problem 10
Dose Concentration effect
D C: Kinetics: what the body does to the drug
C E: dynamics: what the drug does to the body.
1. What is farmacokinetics?
Farmacokinetics is what the body does to the xenobiotica.
Enzymes break the xenobiotica (fe drug) down. You can draw curves for this
(lecture).
A model of a vessel is used to describe kinetics. You need to know two
parameters to describe kinetics:
- Volume of Distribution
- Clearance
The body is seen as a vessel containing blood plasma.
H7 Richard – chemical disposition and toxicokinetics
The disposition and biological reactivity of a toxicant (its toxicodynamics) are the
determining factors in the severity of toxicity. Agents of disposition:
- The duration and concentration of the substance at the site of entry
- The rate of absorption
- Total amount of toxicant absorbed; depends on its physical and chemical
properties and the route of administration.
- The distribution within the body and presence at specific sites
- The efficiency of biotransformation
- The toxicity of the metabolites
- The storage of the toxicant and its metabolites within the body
- The rate and sites of elimination
Toxicokinetic studies determine changes in the blood concentration of a chemical
in the blood, plasma or other tissue over time. They consider thwsi for a chemical
ans a limited number of its metabolites, whereas disposition involved the parent
compound and all of the metabolites. Measured is absorption, distribution,
metabolism and elimination of the chemical.
The studies of toxicokinetics are designed to determine concentration changes of
the chemical and its metabolites over time in blood or plasma and other tissues.
Models of disposition
These are used to describe the movement of toxicants throughout the body over
time. They integrate the processes of distribution, metabolism and elimination.
The body contains a number of compartments or areas (blood, liver, adipose
tissue) where a toxicant can be found at any time. Sveral models have been
described:
- One-compartment model; a toxicant when introduced into the bidy would
be distributed evenly and instantaneously into a single homogenous
compartement; this is the body.
,This assumes that the plasma concentration reflects the changes in tissue
concentrations. The rate of elimination is proportional to the amount of the
toxicant left in the plasma as measured over time and is referred to as first-
order elimination. When graphically displayed, it would show a decrease in
blood concentration as a linear function of time:
Most toxicants however follow a theoretical two- or greater compartment model
of disposition.
- Two-compartment model; the toxicant is distributed from the blood (central
compartment) into a peripheral compartment (for example the kidney)
where it can be eliminated or returned back to the blood.
In this model the concentration increases, reaching a maximal level and then
declines following the time course for elimination from the body. In addition, the
plasma concentration over time yields a curved line in the two-compartement
model rather than a straight line, thus implying more than a single dispositional
phrase.
, In these models a half-life is described as the time required to reduce the blood
or plasma concentration by 50%. This removal of toxicant from the blood is
complex and should not be viewed only as elimination of toxicant from the body.
A half-life needs to be references to the specific tissue (for example blood) that is
being analyzed for its presence because in some tissues it remains for longer or
shorter periods of time. Blood plasma is a good way to monitor the body’s
concentration of a toxicant. However its dissappearnce may represent its uptake
into a second compartement (organ/ tissue), its storage, metabolism or
elimination from the body.
- Multicompartment model
- Physiologically based model
These attempt to stimulate the distribution of toxicants in the body. The body is
viewed as a multicompartment of tissues that are interconnected by blood flows.
The models are defined by physiological volumes, blood flows, partition
coefficients, metabolic rate, age, sex, body weight, percentage of body fat,
ventilation rate and cardiac output.
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