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Examples for PK properties & Dosing adjustment in Renal Failure

Examples for PK properties & Dosing adjustment in Renal Failure
Let’s look at this table. Look at several drugs as an example. When volume distribution is large, by the way the ultimate indicator for drug dialyzability is fraction of the drug lost during dialysis. So when that large, when the contribution is large, then the FL or the fraction loss is small. When the dialysis clearance is small, then the fraction loss becomes larger. Dialysis clearance, of course the larger it is, the higher the fraction of the drug lost during a dialysis. The other factor to look at is the half-life of dialysis and the half-life during dialysis. Let’s look at phenobarbital as an example. From a hundred fifteen hour off dialysis to eight hours during dialysis. And therefore the fraction loss is 30%.
The other example is salicylic acid. The half-life off is 23 hour which is reduced to 4 hours during dialysis, and it’s fraction lost during one hemodialysis session is 51 percent. Data interpretation. We must be careful with their data interpretation. A-V difference could be misleading because it simply indicates that the dialyzer is efficient in removing the drug. If a drug is extensively distributed, that is it has a large volume distribution, then the drug redistribution from the tissue becomes rate-limiting. So in this situation, we should be aware of the concentration rebound. And the ultimate indicator for drug dialyzability is the drug removal as a fraction of dose.
Short dialysis time also limit the amount of drug that can be removed, typically 2 to 4 hours. Recurrent dialysis, however many sessions may lead it to significant drug removal. Let’s look at the venous concentration rebound. Here. During dialysis, the slope is steep. Off dialysis or interdialysis, the drug concentration rebounded. And during dialysis, the half-life drops again. Let’s talk about dosing adjustment in dialysis patient. Now in principle, we would replace the drug lost at the end of dialysis. However, this may be impractical because if the fraction of the drug removed is not significant for example 0.2 or 0.3, then it would be difficult to find the dosage strength to replace the dose at the end of dialysis.
Or to take a large dose at the regular schedule before dialysis. Now this sounds somewhat wasteful of the drug. Or to schedule dialysis at a time when the drug concentration is low and this is to take it advantage of the fact that dialysis is a passive diffusion process. However, this is impractical also because dialysis is typically run on fixed schedule. Now this one is more doable. That is to dose the drug at the end of dialysis. Or to supplement a dose following several sessions of dialysis. And this is the website that you can look up for information.

In this step, Prof. Lee gives the examples for predicted effects of hemodialysis on drug half-life and removal in the overdose setting first, including phenobarbital and salicylic acid.

Following that, for data interpretation, we should notice that the ultimate indicator for dialyzability is drug removal as a fraction of dose, and recurrent dialysis sessions may lead to significant drug removal.

Besides, we can see venous drug concentration rebound from the diagram. The red part means the period during hemodialysis, and the green part means interhemodialysis.

Finally, when facing dialysis patients, we had better dose at the end of dialysis to maintain the drug concentration. Also, we can supplement a dose following several sessions of dialysis.

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Pharmacokinetics: Drug Dosing in Renal Disease

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