Summary: The keys to optimal drug dosing

So the take-home points from that exercise First the new infusion rate or the dosing rate in dose over towel can be determined as a direct linear proportion based on the old CSS which in our example was 12 milligrams per liter or average they say concentration and the new desired values which are the case of our example is 15 milligrams per liter. When converting from an IV to a PO dose, the oral bioavailability requires scaling the oral dose up by dividing the IV dose, by the bioavailability which in the case of our exercise was 0.8.

And lastly to convert a dose over tau dosing rate in milligrams per hour to a specific dosing regimen, we need to try both q 6 hours and q 8 hours and then select the multiple of q 6 or q 8 that best fits the available dosage forms that we have strengths that we have or if there’s an optimal dosing interval which one fits as a multiple maybe there q 6 or q 8. So let’s pause the video one more time and see if you can answer this question.

The time it takes to reach 95% steady-state depends on… A, the value of K. That is a true statement. Now remember we said that the time it takes to reach that 95 percent of steady state is 4.3 half-lives and that is true. However, because half-life is closely related to elimination rate constant number half-life equals 0.693 divided by K. The value of K is also going to impact the time it takes to reach steady state. B says the time it takes to reach 95% steady-state depends on the length of the dosing interval. That is totally false. The length of the dosing interval has nothing to do with the time it takes to reach 95% steady-state.

The only thing that matters is half-life or since half life depends on K, the elimination rate constant. And therefore, C which says that the time it takes to reach study state depends on the size of the dose is also false. The dose and the dosing interval have nothing to do with the time it takes to reach steady state. They will impact the serum concentration, that is achieved at steady state. But not how long it takes to get there. So answer for this question is A. So let’s sum up the keys to optimal drug dosing. There are four things we need to keep in mind that I think it will help you to summarize what we’ve covered in this lesson.

First one is the idea of first-order linearity with first-order drugs that becomes very simple to modify dosing regimens based on the Css or the average Css that we’re trying to achieve for a given patient if we want to double the serum concentration we simply double the dosing regimen or the dosing rate. It’s a straight linear proportion. Second, element is superposition the fact that if we give a drug as a loading dose and also as a multiple dosing regimen or continuous infusion the the drug that is in the patient’s body from different mechanisms doesn’t matter.

All we have to do is identify what the sermon concentration would be from the loading dose or the serum concentration would be from the continuous infusion and add those concentrations together. That represents what the patient’s actual serum concentration would be. It’s a simple addition or superposition. The third is accumulation. Whether we’re giving a continuous infusion or a multiple dosing regimen drug will accumulate over time up to a certain steady-state value with a continuous infusion it starts at zero and it it’s it continues to build up until it reaches a plateau at steady state.

With multiple dosing, the accumulation occurs because at the end of each dosing interval prior to steady state, some drug is left over there’s a seam in concentration and the C max that results from a given dose depends on the amount of increase from that dose plus the Cmin that was left over from the previous dose and that’s how accumulation occurs up to a steady-state where C Max and C min would then be maintained at a plateau for each of them and the last important concept is that of loading versus replacement. In the case of a loading dose when we’re trying to achieve a specific concentration at time zero.

All we’re really concerned about is the size of the concentration that we want to achieve and the volume of distribution the volume of the patient’s tank. It’s a one-time dose to achieve a specific serum concentration. That’s very different from the replacement of drug over time that depends on the rate at which drug is being removed from the tank. It’s kind of like buying bread on the shelves of a store a grocery store. The loading represents the number of loaves of bread it takes to fill the shelves that depends strictly on the amount of shelf space that exists for the loaves of bread.

However, the replacement of the loaves of bread is going to depend on how frequently people are taking loaves of bread off the shelves; how quickly the bread is being eliminated from the shelves. So likewise with a drug we’re gonna load the patient up based on the size of the tank but we’re gonna replace the drug based on how rapidly drug is being eliminated from the tank that’s how we determine the rate of continuous infusion or a multiple dosing regimen rate. If you keep these things in mind, drug dosing should be fairly straightforward and what we’re going to look at in the next lesson is how to use these principles to predict serum concentrations that result from a given dosing regimen.