Parameters used to simulate digoxin CLR
Reduction in filtration and secretion was performed to represent changes in renal impairment. Simulated population representative of the “healthy volunteers” population had an age, weight, and body surface area of 20 years, 81 kg, and 1.98 m2, respectively. Serum creatinine (input parameter of model) was calculated for each scenario using the Cockcroft-Gault equation (Cockcroft and Gault, 1976), based on the target GFR and the age, weight, and body surface area of the population representative.
| GFR | Serum Creatinine Concentration | OATP4C1 Abundance | PTCPGK |
|---|---|---|---|
| ml/min/1.73 m2 | µmol/l | million PTC/g kidney | |
| 136.4a | 76.5 | 1 | 60 |
| 140 | 74.5 | 1.03 | 61.6 |
| 120 | 86.9 | 0.88 | 52.8 |
| 100 | 104.3 | 0.73 | 44.0 |
| 80 | 130.4 | 0.59 | 35.2 |
| 60 | 173.9 | 0.44 | 26.4 |
| 40 | 260.8 | 0.29 | 17.6 |
| 20 | 521.7 | 0.15 | 8.8 |
| 15 | 695.6 | 0.11 | 6.6 |
↵a Relative change in GFR for each scenario was calculated using the value of 136.4 ml/ min/m2 as baseline and applied to the OATP4C1 abundance or PTCPGK parameter.