Abstract: SA-PO644

Drug Dosing During AKI

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Authors

  • Brier, Michael E., University of Louisville, Louisville, Kentucky, United States
  • Aronoff, George, DaVita, Inc., Naples, Florida, United States
  • Gaweda, Adam E., University of Louisville, Louisville, Kentucky, United States
Background

When renal function is rapidly changing during acute kidney injury (AKI), determining the proper dosage for drugs that are renally eliminated becomes difficult. We tested the hypothesis that estimating the creatinine production rate (CPR) combined with measured serum creatinine (Scr) allows us to determine the level of renal function as the estimated glomerular filtration rate (eGFR) to guide in drug dosing.

Methods

Baseline creatinine production was determined by rearrainging the CKD-EPI equation and solving for creatinine generation using the principle that at steady-state the rate of elimination = rate of production. We calculated creatinine production over a range of baseline serum creatinine concentrations for white males, white females, black males, and black females at different ages. Using the change in Scr in 24 hours we are able to determine the integrated eGFR. We then simulated the hourly change in Scr using the estimated CPR and actual GFR to determine delta Scr/24 hours and developed a graphical representation.

Results

The results are shown in the table for CPR (mg/hr) for a 60 year old white male.Dosing information for this patient is shown in the figure with recommendations to dose at a GFR of 0-15, 15-30, and 30-45.Maximum increase in Scr for this patient at no renal function is 1.34 mg/dL/day.

Conclusion

Complex processes occur during AKI that complicate drug dosing. However, estimation of renal function can still occur using routinely obtained Scr measurements that can help in determining drug dosage adjustments.CKD-EPI shows that CPR is decreased in the population as baseline Scr increases.

Creatinine Production Rate (mg/hr)
Baseline ScrWhite/MaleWhite/FemaleBlack/MaleBlack/Female
1.047325437
2.030213524
3.024162719
4.020132316
5.017122014

Example dosing nomogram.