WEBVTT
Kind: captions
Language: en
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The answer of this exercise there it is 200 milligrams every 12 hours. Now let's take a look at why that is.
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If V increases K will decrease and the dosing interval will have to be lengthened or increased proportionately.
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Okay~ Again the change in V causes an opposite change oran inverse change in K and then we have to respond by changing the dosing interval.
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in this case, if K decreases, we're going to lengthen the dosing interval proportionately.
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If V increases the dose is going to have to increase proportionately to keep Cmax and Cmin from changing.
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So we need to change both the dose and the towel to keep Cmax and Cmin from changing when V increases.
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Here's the illustration V doubles. So we double the towel and we double the dose.
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We go from 100 milligrams q6 every 6 hours to 200 milligrams every 12 hours. There it doesn't change but K did change because of the volume change.
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K goes from 0.2 to 0.1. Volume goes from 25 liters to 50 liters. So you can see in the red curve.
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The fact that we doubled the dose compensated for the fact that the volume doubled and the concentration at x 0 did not change.
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But the elimination rate constant is decreased and therefore the serum concentration falls less rapidly.
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So by doubling the dosing interval we enable the minimum the Cmin to remain at 1.7 and by doubling the dose to compensate for the the doubling of the volume
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we keep C max the same at 5.7. C average steady state would also stay the same at 3.3 and the area under the curve because we doubled the dose.
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And the clearance did not change the area under the curve will double.
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Now if we respond to a doubling of the volume by simply doubling the dose and this was what would seem intuitively obvious.
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If volume doubles then simply double the dose and that should compensate for it.
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But that ignores the fact that the elimination rate constant drops in half. So the red curve illustrates what would happen if we compensated
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for a doubling of the volume of distribution simply by doubling the dose. In this case we go from 500 milligrams q12 to 1,000 milligrams g12.
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In this case Cmax will increase we've increased the dose again but we have not increased the dosing interval.
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So Cmax will increase, Cmin will increase
because we've not allowed more time for the serum concentration to fall despite the decrease in the elimination rate constant.
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Our C max minus C men will
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not change because we compensated for
the change in volume by doubling the
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dose so dose over volume would not
change it's still going to be 10
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milligrams per liter C average steady
state would double C our steady state is
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dose divided by tau we double the dose
without changing tau and there's no
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change in clearance C average steady
state will double and the area under the
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curve would also double again we've
doubled the dose we've not changed the
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clearance so you can see that the C max
will increase due to the effect of
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volume change on K now let's consider
what happens when the clearance and also
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K drop in half and so we double the top
so now we go from 500 milligrams every
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12 hours to 500 milligrams every 24
hours with the clearance that is
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dropping in half when we do that we can
see that the lengthening of the dosing
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interval compensates
for the decrease in clearance the red
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curve and sees the drug being eliminated
much less rapidly and therefore the
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longer dosing interval allows enough
time for the Sarah concentration to fall
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to the original cement so when we
compare the results there's no change in
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the C max there's no change in the C min
we didn't change dose over volume and we
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allowed extra time in the dosing
interval to compensate for the decrease
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in K and in clearance C max minus C men
would not change because dose and volume
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did not change C average steady state
would not change because dose over tau
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did not change nor did the clearance
change so what we have here is an area
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under the curve that would double from
100 to 200 so the change in tau
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essentially neutralizes the change in
clearance and in K we haven't changed
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the dose so the the average steady state
concentration would remain the same
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because we haven't changed the dose and
the tau and the clearance would cancel
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each other out see if you can answer
this question why does area under the
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curve not change when volume changes
first of all let's consider a in
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comparison to the equations that we have
we know that area under the curve is
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equal to the concentration at time zero
divided by K and also dose divided by
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clearance but now we're introducing
volume into this equation it's not
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specifically listed as such but we know
that a change in volume causes a change
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in K and K is part of our area under the
curve equation but that's not the whole
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story because area under the curve is
not going to change when V changes we
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also know that a change
in volume will cause a change in the
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concentration at time zero so
essentially what we have is a change in
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volume causing a change in both
parameters concentration at time zero
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and K and they essentially cancel each
other out so you can't just look at one
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aspect of the impact of volume when you
put the answer to a and B together
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it essentially identifies why there's no
change in area under the curve when
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volume changes C is a false statement a
change in V does not cause a change in
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clearance clearance is not dependent on
volume of distribution so the answer is
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D both a and B explain why area under
the curve does not change when volume changes