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Skip to 0 minutes and 11 seconds This slide is kind of busy and I don’t expect you to be able to see it. But this slide actually is the numerical basis for the previous graph. Here is the knr. Here is the kn. And the third column is a Knr to K ratio in decreasing order. And for category L, those are the drugs was the small or the very minimum knr to Kn ratio. Indicating those drugs are very extensively excreted by the kidneys. So K ratio can be derived for different categories of drugs. However, we can also take a general approach to the K ratio. And this slide shows the derivation of K ratio based on kidney function and fraction of the top excreted unchanged.

Skip to 1 minute and 29 seconds Now without going through the detail. I will simply give you the answer. And that answer is or gives us the estimate for the initial dose in uremic patient which says the dose in uremic patient is equal to dose in the normal patient times 1 minus fe times 1 minus KF Here, fe is the fraction of drug excreted unchanged in the urine. KF is kidney function expressed as a fraction of the normal. Assumining in normal GFR of 100 to 125 mils per minute. Now the creatinine clearance for the uremic patient can be calculated by Cockcroft equation or by the MDRD equation using serum creatinine which is more readily available in clinical situation.

Skip to 2 minutes and 35 seconds So here let’s look at the one example for the general approach. The question is here. Your question is what is your recommended dose as a percent of normal adult dose for a drug that is 75 percent excreted unchanged by the kidneys in the uremic patient whose creatinine clearance is 10 mils per minute? Assuming normal GFR is 100 meters per minute and that the drug metabolism is not affected by uremia. So we know the overall k elimination rate constant is Kr plus Knr. So what is Kr for this patient? kr for this patient is point 1 times 75 percent. Because his kidney function is 10% and the drug is 75% excreted unchanged by the kidney. Therefore, Kr is 0.075 of K.

Skip to 3 minutes and 46 seconds On the other hand, what is knr the non renal excretion rate constant? It is unchanged in renal failure or in uremic. Therefore it keeps the whole 0.25 of K that is 1 times 25 percent because the drug is 25% metabolized. Therefore K ratio, as a fraction of the normal is 0.075 plus 0.25 and that gives you 0.325. Therefore the dose is in this uremic patient is thirty-two point five percent of the normal dose.

General approach to K ratio : Example 1

In this step, Prof. Lee explains the general approach to K ratio and how to estimate initial dose in uremia.

In the first slide, those drugs in category L have the small or the minimum knr to Kn ratio, indicating that they are very extensively excreted by the kidneys.

Following that, we can learn that initial dose in uremia is closely related to fraction of drug excreted unchanged in the urine (fe), and kidney function as a fraction of normal (KF).

Finally, we need to understand the relationship between K, Kr. and Knr. Therefore, we can know the accurate K.

Do you know the value of fe in the example? Please leave your answer below.

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This video is from the free online course:

Pharmacokinetics: Drug Dosing in Renal Disease

Taipei Medical University