Skip to 0 minutes and 16 secondsHow is that done? Well based on the AUC 24 which is the area under the curve for 24 hours. In this example, if a patient is receiving a dose of 500 milligrams every eight hours and the clearance is four liters per hour, we could see that the area under the curve for 24 hours is the daily dose which in this case will be 1500 milligrams or 500 milligrams three times a day divided by the clearance 1500 divided by 4 is an area under the curve for 24 hours or AUC 24 of 375 milligrams hours per liter.
Skip to 0 minutes and 59 secondsNow the area under the curve for each dose that the patient receives is dose over clearance which would be 500 milligrams divided by 4 liters per hour which is 125 milligram hours per liter. So the there's consistency here. The area under the curve for each dose is 125 and the patient receives 3 doses a day so the area under the curve for 24 hours is simply 125 times 3 or 375 milligrams hours per liter. The vancomycin clearance can be estimated using the equation shown 0.047 times the patient's crediting clearance that would be in milliliters per minute plus 0.92.
Skip to 1 minute and 53 secondsNow it's actually a modification of the equation that's used in for the Wanfang dosing chart that I showed you on the previous slide which is 0.79 times the crediting clearance and milliliters per minute plus 15 point four However, for use in the AUC 24 equation the credit clearance has to be in liters per hour. So it's an it's necessary to convert milliliters per minute to liters per hour and that's done by multiplying the clearance in milliliters per minute by 0.06. So when you multiply the 0.79 by 0.06 you get 0.047 and 15.4 multiplied by 0.06 gives you 0.92. So, these equations are essentially the same thing.
Skip to 2 minutes and 49 secondsThe therapeutic targets for vancomycin, for efficacy, what we like to achieve is an area under the inhibitory curve greater than 400. Remember area under the inhibitory is the AUC 24 divided by MIC. So as the MIC of a pathogen increases, the area under the curve 24 hours is going to have to increase in order to still maintain an AUIC above 400. It's going to take twice as much drug to treat a patient with an MIC with a pathogen that has an MIC2 than an MIC of 1. What we're concerned about is the area under the curve above the MIC and that has to be greater than 400.
Skip to 3 minutes and 46 secondsWhen we consider the potential for toxicity nephrotoxicity is a greater risk if the patient has an AUC 24 greater than 700 milligram hours per liter. So when we're focusing in on efficacy on treating the infection we're focusing in on the AUIC the area under the curve portion that's above the MIC but when we're concerned about nephrotoxicity its the total area under the curve that we're concerned about and that needs to be ideally less than 700 milligram hours per liter which corresponds to a steady-state concentration of less than 28 milligrams per liter.
Skip to 4 minutes and 33 secondsArea under the curve remember for 24 hours is the total daily dose divided by the clearance in liters per hour and the concentration at steady-state is area under the curve divided by 24 because there's 24 hours in a day.
Skip to 4 minutes and 56 secondsSo to determine a vancomycin dosing regimen based on area under the inhibitory curve, we shoot for an area under the inhibitory curve of greater than 400 and an AUC 24 of less than seven hundred milligram hours per liter. To calculate the daily dose in milligrams per day, we simply rearrange the equation to get dosed 24 dose per day equal AUIC, area under the inhibitory curve times the clearance of vancomycin ain liters per hour times the MIC. Now this is a another dosing chart that was developed by Wanfang hospital and it shows the daily dose that should be given to a patient when we're going to use AUC dosing based on whether the MIC is 0.5 1 or 2.
Skip to 5 minutes and 49 secondsYou can see that as the MIC increases from 1 to 2 the total amount of drug essentially doubles and you see that the vancomycin clearance equation there shown at the bottom of the chart. Now what's interesting is that even when we're using area under the curve as our target dosing approach, we monitor the patient by evaluating the trough concentrations and there is some leeway when we have a daily dose identified. There is some leeway in the specific dosing regimen that that daily dose would be represented by. For example, if the daily dose that the patient needs to receive is 3,000 milligrams a day, we could give the patient's 1500 milligrams every 12 hours or 1000 milligrams every 8 hours.
Skip to 6 minutes and 42 secondsLook at the difference in terms of the peak and trough serum concentrations. When we do that, by giving the patient 1000 milligrams every eight hours we actually obtain a higher trough than when the patient receives 1500 milligrams every 12 hours. Even if we dose by AUIC the C trough is what's monitored and by selecting a smaller dose with a shorter interval the C max is going to be a little bit smaller and the C min or the C trough is going to be a little bit higher. So there's a greater likelihood that we're going to achieve a trough in the therapeutic range in the more aggressive therapeutic ranges that exist today of ten to fifteen or fifteen to twenty.
Skip to 7 minutes and 39 secondsIf you choose a larger dose with a longer interval is a greater likelihood that even though the dose is adequate, the trough level might drop below that target level of at least ten for a mild to moderate infection. See if you can answer this question
How to determine a Vancomycin dosing regimen based on AUIC?
Prof. Brown uses an example to describe how to adjust Vancomycin dosing based on AUC (24hr).
We can understand AUC therapeutic targets for Vancomycin, including maximizing efficacy and minimizing nephrotoxicity.
He provides a dosing chart developed by Wanfang Hospital, which reveals the daily dose that should be given to a patient.
What is the relationship between dose, AUIC, and MIC? Please leave your answer below.
Do you find any dosing difference(s) between your hospital and Wanfang Hospital? And what is your opinion? Please share your opinion below.
Prof. Daniel L. Brown