Abstract: SA-PO644
Drug Dosing During AKI
Session Information
- Pharmacokinetics, Pharmacodynamics, Pharmacogenomics
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
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 Scr | White/Male | White/Female | Black/Male | Black/Female |
| 1.0 | 47 | 32 | 54 | 37 |
| 2.0 | 30 | 21 | 35 | 24 |
| 3.0 | 24 | 16 | 27 | 19 |
| 4.0 | 20 | 13 | 23 | 16 |
| 5.0 | 17 | 12 | 20 | 14 |
Example dosing nomogram.