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Language: en
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Intermittent infusion dosing,
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we can morph two dosing equations that you should already be familiar with
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to determine that the calculations
that should be used in minimum glycoside dosing.
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The infusion calculation that you are familiar with
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the rate of infusion times 1 minus e to the minus KT where T is the time of infusion divided by the clearance
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that determines the concentration that exists at any point in time T prior to steady state.
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When we administer vancomycin and aminoglycosides considering aminoglycosides in this case
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the drug is administered by infusion.
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So this part of the equation will tell us the concentration that will will exist after the infusion is complete.
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However that infusion is given as a multiple dosing intermittent regimen
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and the Cmax for an intermittent regimen is dose over volume times 1 minus e to the minus K tau
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or T is now the dosing interval.
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So if we morph these two equations together for multiple dosing of aminoglycosides
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when the drug is going to be administered by infusion, what we see is that the C peak at steady state
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would be equal to the rate of infusion times 1 minus e to the minus K T
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where T is the time of infusion over the volume of distribution times the elimination rate constant
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times 1 minus e to the minus K tau.
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What we see is that V times K essentially replaces the clearance,
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that's in the continuous infusion equation.
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And if we multiply that portion of the morphed equation by e to the minus K T Prime
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that provides for the percent of drug that's remaining after that time interval from the end of the infusion
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to the measurement of the peak level.
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So what you see is is a very complicated appearing equation.
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That's really not very complicated when you stop and consider
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how it it really combines two equations that you're already quite familiar with.
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Step one, in analyzing Aminioglycoside serum levels is simply to take the measured serum concentrations
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to determine the patient's elimination rate constant and volume
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based on the current dosing regimen.
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The elimination rate constant as we've already discussed in a previous lesson,
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you simply take the natural log of the measured peak over the measured trough
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and divide that by the time interval between those two to determine the elimination rate constant.
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And volume is simply a rearrangement
of the equations shown in the previous slide
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where volume is equal to the rate of infusion
times 1 minus e to the minus KT
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where T is the time of infusion divided by the C peak times the elimination rate constant
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time it's 1 minus e to the minus K tau or T is the dosing
interval times e to the minus KT Prime.
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Keep in mind, when you're calculating the volume
of distribution of an aminoglycoside patient
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that it's not the dose that's in this equation.
It's the rate of infusion.
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So if a patient is receiving 80 milligrams as a dose, that's administered over 30 minutes or 0.5 hours
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the rate of infusion would actually be 160 milligrams per hour, not the 80 milligram dose that's given.
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It's important to keep track of what the three different time intervals represent in this equation.
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Step two in the aminoglycosides serum level analysis process
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is to determine the new dosing regimen the
rate of infusion and the tau the dosing interval
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based on the desired serum levels and the
patient's elimination rate constant and volume
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that were just determined.
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So to do this you would the Tau would be equal to the natural log of the desired peak
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over the desired trough divided by the patient's elimination rate constant that was just determined.
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The rate of infusion would be equal to the C peak and again this is an algebraic rearrangement
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of the equation on the previous slide.
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The C peak times the patient's volume times the elimination rate constant times 1 minus e to the minus K tau or tau is the dosing interval
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divided by 1 minus e to the minus K T where T is the time of infusion.
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Generally either 0.5 hours that puts a 30-minute infusion or 1 it's a 1 hour infusion,
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times e to the minus KT prime where T prime is the time interval
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from the end of the infusion to the measurement of the peak level.
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Now oftentimes this is done automatically
using a computer or an online program,
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but I think it's important for pharmacists even
if you're using a program to crank these calculations,
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it's important for pharmacists to understand
the processes that are taking place as these
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equations are being calculated.
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Another important consideration is when to start the new dosing regimen?
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In other words, how long will it take for the peak level on the old dosing regimen
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the last peak that was measured to drop down to what the new trough level would be.
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In order to do this, that this time to the next dose would be the natural log of the C peak that was measured
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on the old dosing regimen, divided by the C trough that were shooting for with the new regimen.
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And all of that divided by the patient's elimination rate constant.
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Okay the first dose of the new regimen is due
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when the concentration drops to what the new trough is expected to be.
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I learned this the hard way when I was a resident.
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I had a case in which I was paged in the middle of the night
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patient was receiving 80 milligrams every eight hours of an aminoglycoside
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and I calculated based on the patient's serum concentrations
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that the dose needed to be changed to a hundred milligrams to twelve hours.
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Problem was when I relayed that information to the physician,
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I didn't specify when the new dosing regimen should be started.
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Physician wrote in order to discontinue the 80 milligrams every eight hours
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and start 100 milligrams every 12 hours didn't specify a time
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and the pharmacists the process the order just put it into the computer as is
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and what ended up happening
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was the patient received an 80 milligram dose in just a couple hourse of late
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couple hours later received the first 100 milligram dose in the new regimen.
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And I learned a very valuable lesson at that point
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it's give some thought when you're going to change a dosing regimen;
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give some thought to when the new dose should be given in relation to when the last former dose
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had been administered and make sure that's clearly communicated to the prescribed
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what I should have said is discontinue the 80 milligrams every eight hours
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start 100 milligrams every 12 hours at nine o'clock this morning provided a specific time
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and in order to do that you have to calculate the optimal time to begin it's using this equation shown on the slide.