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Effects of Renal Failure on ADME

Effects of Renal Failure on ADME
Hello everybody, this is professor Lee, from Taipei medical university. Welcome to the class. Today’s topic is dosing regimen and the therapeutic drug monitoring in renal failure. First let’s look at the effect of renal failure on absorption, distribution, metabolism and excretion. First, renal failure on absorption. Renal failure generally decreases drug absorption because of the following reasons. Decreased mesenteric blood flow associated with renal failure with decreased absorption or bio-availability of the drug. Decreased GI motility would also tend to decrease absorption. Absorption type, Antacid could potentially reduce drug absorption, portal proton pump inhibitors.
Because pH dependent effect on absorption depending on whether the drug is an acid or a base Drug interaction due to multiple drug administration in renal failure would also change bioavailability in different ways. How about renal failure on distribution? The primary effect is that decreased plasma protein binding would increase the volume of distribution. Now this is due to competition for protein binding from accumulated fatty acid and other metabolic product. Decreased renal blood flow would also tend to decrease volume of distribution. Decrease the binding due to proteinuria would increase volume of distribution. Decreased tissue uptake would decrease volume of distribution. Change of electrolyte and the fluid balance would affect drug distribution in the extracellular fluid.
And in fact on volume distribution could be either way depending on whether the drug is water-soluble or lipid-soluble. Renal failure effect on metabolism. Renal failure does not usually affect drug metabolism until the very end stage So dosing adjustment in renal failure is not necessary for drugs that are extensively metabolized. So there is one less thing to worry about. However, if the drug is metabolited in the kidneys, then the metabolic clearance of the drug could be reduced because of the decreased renal blood flow or decreased enzymatic activity in the kidneys. How about the effect on clearance and half-life? Decreased GFR would decrease renal clearance. Decreased tubular secretion would also decrease renal clearance. Decreased reabsorption however would increase the renal clearance.
The net effect of those three components with decreased renal clearance. And therefore there’s a decreased total clearance. And as a result, the elimination half-life is prolonged. How about renal failure on pharmacodynamics? The effect on receptor is unclear whether the receptor expression, receptor sensitivity, receptor translocation. And therefore, we assume same therapeutic concentration for renal failure patient as those with normal kidney function

This week, we will learn dosing regimen and TDM in renal failure.

Prof. Lee clarifies the effects of renal failure on ADME in this step.

To begin with, we should know ADME, including absorption, distribution, metabolism, and excretion.

For absorption, renal failure generally decreases it. For distribution, renal failure decreases plasma protein binding due to competition for accumulated fatty acids and other metabolic products.

For metabolism, renal failure does not usually affect drug metabolism until the very end-stage. Prof. Lee will also explain the effects of renal failure on clearance, half-life, and pharmacodynamics as well.

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Pharmacokinetics: Drug Dosing in Renal Disease

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