WEBVTT
Kind: captions
Language: en
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Let's consider the take-home points from
this exercise.
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First of all, when a loading dose is given to start therapy the usual goal is to achieve a concentration at time zero
00:00:26.040 --> 00:00:27.560
after the loading dose.
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That is about the same as the projected stay state concentration.
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That's our ultimate goal.
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Once you have the target concentration at time zero
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the loading dose is simply the amount of drug that will produce that concentration
00:00:42.180 --> 00:00:43.860
in the given volume.
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It's filling the tank
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Let's consider now a multiple dosing
regimen
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where we're trying to achieve a specific average steady-state concentration from intermittent dosingㄡ
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A mainus dosing regimen can either involve the rate of infusion
00:01:02.860 --> 00:01:08.860
such as a continuous infusion of perhaps twenty milligrams per hour as a continuous infusion
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or it can be a dose given at certain intervals
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and the designation that we use for dosing interval is Tau
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or the Greek letter tau(τ)
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In this case the example is 200 milligrams every six hours.
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In either case what we're concerned about is the rate at which drug is being administered to the patient.
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So for a continuous infusion it's fairly obvious we're giving a rate of so many milligrams per hour.
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In the case of a multiple dosing regimen or intermittent dosing regimen,
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we have to divide the dose by the Tau.
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So in the case of 200 milligrams every six hours,
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the average dosing rate would be thirty three point three milligrams per hour.
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The average steady-state concentration is the dosing rate in milligrams per hour divided by the clearance.
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So it's very similar to a continuous infusion where the equation on the Left shows that Css
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is equal to the rate of infusion divided by clearance.
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When we're talking about the average steady-state concentration during multiple dosing,
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its dose divided by tau or the dosing rate divided by clearance
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In a sense both of these equations
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have the rate out the rate at which drug is being eliminated on the left and the rate in on the right,
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or the continuous infusion the rate out is the Css times the clearance
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and that is equal to the rate at which the drug is being infused the Rinf.
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For a multiple dosing regimen it's the average stay state concentration times the clearance
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is the rate out and the rate in is dose over
tau
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or the dose divided by the dosing interval how many milligrams per hour
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on average are being administered to the patient.
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Now when we convert a dosing
rate a dose over tau,
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we complete that calculation we know that a certain number of milligrams per hour
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need to be given to the patient.
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If it's an intermittent dosing regimen, we need to break that down into a specific dose
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and dosing interval or a dose and a Tau.
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Now let's assume for the sake of example
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that the dosing rate we need to achieve is 50 milligrams per hour.
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Now we have to consider what the options are for dosing this drug
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what strengths is the drug available
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and is it available in 200 milligrams, 250 milligrams, 300 milligrams, 400 milligrams.
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We're going to have to use a dosing rate that's compatible to the strengths of the drug that are available
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and there might also be an optimal dosing interval
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based on the pharmacodynamics or the pharmacokinetics of the drug.
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That we're shooting for and that's going to affect the the specific dosing regimen
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that we select for a given dosing rate.
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But once we know what our limitations are and coming up with a specific dosing regimen,
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the way to convert a dosing rate in milligrams per hour to a specific regimen is very simple.
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We assume two options.
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We're either going to start with Q six hours or every six hours as our base interval
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In which case for a 50 milligram per hour dosing rate that would be 300 milligrams every six hours
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or we try every eight hours in which case a 50 milligram per hour rate would be four milligrams every eight hours.
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Now the beauty of going with q6 and q8 is that every possible practical dosing interval
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is a multiple of one of these two values
in the case of q6,
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if the best dose would be 600 milligrams or the best dosing interval would be Q12,
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we can go with a 600 milligram dose.
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Based on just scaling up the 300 milligrams q6,
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if we scale it from the q8 dose of 400 milligrams
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we can go with every 4 hours which would be 200 milligrams every 4 hours.
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Or either the q6 or the q8 regimen would make it easy to determine a q24 regimen
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either multiplying the 300 milligrams by 4 to get 1200 milligrams
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or the 400 milligrams by 3.
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there'd be three doses once a day versus three
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one dose once a day being the same as three doses every eight hours at 1200 milligrams.
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So we can identify the most practical dosing regimen
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starting with q 6 and q 8 and multiplying them by the dosing rate
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that we initially determined.
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Let's pause again for answering of a question.
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Okay, you've answered this question a dosing regimen of 400 milligrams every eight hours,
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produces the same C average steady state as a dosing regimen of...
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Now we know right off the bat that if we've got a dosing regimen of 400 milligrams every eight hours
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we're talking about a dosing rate of 50 milligrams per hour.
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So whatever dosing regimen the patient receives in order to keep the C average steady state the same,
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we're gonna have to use the same dosing rate in milligrams per hour.
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300 milligrams q 6 is indeed 50 milligrams per hour.
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Likewise 600 milligrams q 12 is also 50 milligrams per hour
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but 900 milligrams every 24 hours is not 50 milligrams per it would have to be 1,200 milligrams every 24 hours .
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So the answer to this question is D.
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A and B are correct but C is not.
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Now let's explore the challenge of coming up with a multiple dosing regimen
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that's based on Cmax and Cmin,
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in a specific C Max and C min rather than C average steady-state.
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In order to come up with a multiple dosing regimen shooting for a specific C Max and C min,
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we first have to know what the target C Max and C min is,
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and we have to know both the elimination rate constant and the volume.
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Now what we're going to discover as we continue through this course
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is that K relates more directly to the dosing interval to the tau
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and volume relates more directly to the dose
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when we're looking for a C average steady state
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and we don't care about C Max and C men
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we can use clearance which is the combination of K times V
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but when we want to tease out a specific C Max and C min
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we need to keep the elimination rate constant and the volume separateㄡ
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Such that the elimination rate constant gives us a clue about the best dosing interval
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and the volume gives us a clue as to the best dose.
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So the first thing we would do is calculate the dosing interval
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and round it to a practical number.
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Now the equation that we've already covered the time is equal to the natural log of c1 over c2
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divided by K.
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Now specifically our time is tiled the dosing interval
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and c1 and c2 represent the maximum concentration and the minimum concentration.
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The result during this dosing interval and they're divided by the patient's elimination rate constant.
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So this would give us the dosing interval based on the patient's K
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they would achieve the specific C Max
and C men that we're looking for.
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We were then round that off to a practical number the closest four six eight twelve 24 hours
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whatever that may be.
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We would then calculate the dose.
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And thedose is represented by the the c-max at steady state is produced by the dose divided by the volume
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divided by one minus e to the minus K tau.
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Now let's take a closer look at that.
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C at time zero we've said is the dose divided by volume.
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So C max we can think of it as the C at time zero
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dose divided by volume, divided by one minus e to the minus K tau.
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1 minus e to the minus K tau is the factor that determines
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the comparison between the concentration that results from an individual dose a single dose
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at time zero to what that same dose given intermittently would produce
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as a maximum steady state concentration at time tau
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we see the Tau in the denominator of that equation
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so whatever time the dosing interval is
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we plug that in and that would tell us
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how the extent to which the drug is going to accumulate from the serum concentration after one dose
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to the multiple dosing an intermittent dosing schedule.
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And we can see then that the dose would actually be calculated
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by taking the C max concentration times the volume times the factor 1 minus e to the minus K tau.