1. Changes in total drug clearance with declining kidney function relates to the extent of drug clearance by the kidney.
Changes in total drug clearance with declining kidney function relates to the extent of drug clearance by the kidney. Representation on the basis of Equation 3 for drugs with three different pharmacokinetic profiles. Here, Drug A is 100% cleared by the kidney, and therefore, it is predicted that a 50% decrease in GFR will correlate with a 50% decrease in total clearance, prompting a 50% decrease in dose or doubling of the dosing interval to maintain the same mean plasma concentration. Drugs from many classes can be represented: for example, antibiotics (A: β-lactams or aminoglycosides, B: macrolides, and C: fluoroquinolones), anticoagulants (A: dabigatran, B: warfarin, and C: rivaroxaban), and β-blockers (A: atenolol, B: metoprolol, and C: bisoprolol). Unfortunately, this representation is an oversimplification, because it does not consider changes to nonrenal clearance in kidney disease that occur with some drugs as discussed in the text.
Tom N. Lea-Henry et al. CJASN 2018;13:
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