1. Dose adjustments in patients with CKD are based on the change in the concentration-time profile for the drug of interest.
Dose adjustments in patients with CKD are based on the change in the concentration-time profile for the drug of interest. Compared with patients with no kidney disease, those with advanced CKD receiving oral dihydrocodeine (upper panel; substrate of CYP2D6 and CYP3A4) showed a decrease in clearance and an increase in the mean area under the concentration–time curve and Cmax of 70% and 29%, respectively. To achieve concentrations similar to those in patients without kidney disease, the dosing interval should be prolonged but the dose does not need to be changed. In contrast, for oral repaglinide (lower panel; substrate of CYP3A4, CYP2C8, and organic anion transporting polypeptide OATP1B1, in patients with advanced CKD the mean area under the concentration–time curve and Cmax increase 232% and 82%, respectively compared with patients with no kidney disease. Here, to achieve plasma concentrations similar to those in patients without kidney disease, both the dosing interval should be prolonged and a lower dose should be prescribed. Figure panels are approximate representations of data published by Barnes et al. (11) and Marbury et al. (12).
Darren M. Roberts et al. CJASN 2018;13:
©2018 by American Society of Nephrology