El Helalyaالمؤسسة
تاريخ التسجيل : 08/08/2008
 |  موضوع: AlL AbOuT >>>>DRUG ELIMINATION >>>IT IS REALLY GOOD> الأحد 6 يونيو 2010 - 23:32 | |
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El Helalyaالمؤسسة
تاريخ التسجيل : 08/08/2008
| | موضوع: رد: AlL AbOuT >>>>DRUG ELIMINATION >>>IT IS REALLY GOOD> الأحد 6 يونيو 2010 - 23:33 | |
| Aspirin
Elimination
Slide of aspirin plasma concentration as a function
of
time after 0.25, 1 or 2g. At higher doses the metabolism of aspirin
is
reduced by saturation. The elimination rate constant (as represented
by
the slope) is reduced
Multiphasic
Drug Elimination
Slide of pentobarbital plasma
concentration
versus time illustrating the multiphasic distribution
pattern. From a
plasma concentration time curve it may appear that this
drug is
rapidly eliminated from the body. Actually little of the drug is
eliminated with much of it being distributed in various tissues of the
body.
Here distribution is a major factor affecting the overall kinetics
of this drug. By looking further we can see the real picture
Tissue Concentration versus Time
Slide
showing pentobarbital concentrations in various tissues. This
illustrates
the slow distribution of some drugs into and out of various
tissues.
Brain and other rapidly perfused tissues rapidly lose drug
while
other tissues are building up drug concentrations. Eventually
significant
amounts of drug will be collected in fat tissue from which
it may
only slowly be removed. The green line represents concentrations
in
adipose tissue (poorly perfused), the red line represents
concentrations
in viscera (highly prefused lean tissue), the yellow line
represents concentrations in lean tissue (poorly perfused) and the blue
line represents concentrations in blood
Distribution
Slide
showing other distribution
mechanisms. Methods by which drug is kept in
the body for extended
action. pH, protein binding and fat storage are
three major
processes by which drug may be kept within the body. These
are
mechanisms by which drugs can be distributed throughout the body,
protected
from elimination, and cause a more prolonged activity
IV Bolus One Compartment Model
Definition
Pharmacokinetics
is the study of
drug and/or metabolite
kinetics in the body. It deals with a
mathematical description
of the rates of drug movement into, within
and exit from the body. It
also includes the study of drug
metabolism or biotransformation rates.
The body is a very complex
system and a drug undergoes many steps as it
is being absorbed,
distributed through the body, metabolized or excreted
(ADME
The drug
also interacts with receptors
and causes therapeutic and/or toxic
responses. Although the details
of drug kinetics are complicated it is
fortunate that we can often
approximate drug kinetic processes using
"simple" mathematical
models
Assumptions
We will
start the course with a one compartment -
linear model. Also, we
will first consider drug kinetics after a rapid
intravenous
injection, an IV bolus injection. According to this model we
will
consider the body to behave as a single well- mixed container. To
use
this model mathematically we need to make a number of assumptions.
One compartment
The
drug in the blood is in rapid equilibrium
with drug in the
extravascular tissues. The drug concentration may not
be equal in
each tissue or fluid however we will assume that they are
proportional
to the concentration of drug in the blood at all times.
This is not
an exact representation however it is useful for a number of
drugs
to a reasonable approximation. Rapid
Mixing
We also need to assume that the drug is mixed
instantaneously
in blood or plasma. The actual time taken for mixing is
usually
very short, within a few of minutes, and in comparison with
normal
sampling times it is insignificant. We usually don't sample fast
enough
to see drug mixing in the blood. Linear
Model
We will assume that drug elimination follows first
order
kinetics. First order kinetics means that the rate of change of
drug
concentration by any process is directly proportional to the drug
concentration
remaining to undertake that process. Remember first order
kinetics
is an assumption of a linear model not a one compartment model.
If
we have a linear if we double the dose, the concentration will
double
at each time point
Linear Model -
First Order Kinetics
First-order
kinetics To
illustrate first order kinetics we might consider what
would happen if
we were to give a drug by iv bolus injection,
collect blood samples at
various times and measure the plasma
concentrations of the drug. We
might see a steady decrease in
concentration as the drug is eliminated
Rate versus Cp
If
we measure the slope of this curve at a number of times we are
actually
measuring the rate of change of concentration at each time
point,
ΔCp/Δ, represented by the straight line
Now if we plot this rate of change versus the plasma
concentration,
for each data point, we will get a straight line when
first order
kinetics are obeyed
as below
This behavior can be expressed mathematically as
One Compartment Model
دمتم
فى امان الله  الموضوع : AlL AbOuT >>>>DRUG ELIMINATION >>>IT IS REALLY GOOD> المصدر :منتديات تقى الإسلامية الكاتب: El Helalya |
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الجنه تنادينيالاشراف العام
تاريخ التسجيل : 16/05/2010
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واسلاماهالمراقبة العامة
تاريخ التسجيل : 23/06/2009
| | موضوع: رد: AlL AbOuT >>>>DRUG ELIMINATION >>>IT IS REALLY GOOD> الجمعة 8 يوليو 2011 - 19:57 | |
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