Table 3.
Pharmacodynamic Prediction of Creatinine Change Over Time Dependent on Baseline Creatinine and Cumulative Acetaminophen Exposure Over 3 Days (AUC0-72h)
| Baseline Serum Creatinine (mg/dL) |
Probability of Belonging to Subpopulation 1 (%)a |
||||
|---|---|---|---|---|---|
| No Acetaminophen |
AUC0-72h 100 mg × h/L |
AUC0-72h 200 mg × h/L |
AUC0-72h 300 mg × h/L |
AUC0-72h 500 mg × h/L |
|
| 1.25 (110.5μmol/L) |
10.0 | 1.46 | 0.199 | 0.0266 | 0.0005 |
| 1.50 (132.6μmol/L) |
16.0 | 2.49 | 0.341 | 0.0458 | 0.0008 |
| 2.00 (176.8μmol/L) |
36.0 | 7.00 | 1.00 | 0.135 | 0.0024 |
| 2.50 (221μmol/L) |
62.4 | 18.2 | 2.89 | 0.397 | 0.0072 |
| 3.00 (265.2μmol/L) |
83.0 | 39.6 | 8.08 | 1.16 | 0.0211 |
Pharmacokinetic-pharmacodynamic (PK–PD) mixture model of observed creatinine described 2 subpopulations, where subpopulation 1 had an increasing creatinine over time and subpopulation 2 had a decreasing creatinine over time. All simulations were based on the developed final model, including enrollment creatinine and acetaminophen AUC0-72h as predictors of the mixture probability. Full details of PK–PD modeling are shown in the Supplementary Material. Conversion from creatinine mg/dL to µmol/L: multiply by 88.4.
Abbreviation: AUC, area under the acetaminophen drug concentration–time curve.
aIncreasing serum creatinine over time.