TABLE 2.
Summary of plasma PK parameters of FEP and ZIDa
| Parameter by drug | Data by renal impairment vs controls |
ESRD on HD |
||||||
|---|---|---|---|---|---|---|---|---|
| Mild |
Moderate |
Severe |
||||||
| Impairment (n = 6) | Control (n = 6) | Impairment (n = 6) | Control (n = 6) | Impairment (n = 6) | Control (n = 6) | Impairment (n = 4)b | Control (n = 6) | |
| FEP | ||||||||
| AUC0–t (h µg/ml) | ||||||||
| Mean | 479.0 | 351.9 | 922.9 | 307.0 | 698.3 | 331.1 | 1,247.8 | 293.2 |
| SD | 92.4 | 62.6 | 228.8 | 57.3 | 255.0 | 63.2 | 304.3 | 69.5 |
| AUC0–∞ (h µg/ml) | ||||||||
| Mean | 483.6 | 355.1 | 932.0 | 310.8 | 749.1 | 340.5 | 1,581.6 | 298.4 |
| SD | 92.8 | 63.5 | 231.8 | 57.8 | 305.1 | 71.0 | 585.9 | 69.2 |
| Cmax (µg/ml) | ||||||||
| Mean | 132.1 | 126.2 | 134.2 | 116.8 | 64.0 | 125.3 | 499.1 | 113.2 |
| SD | 25.3 | 32.6 | 18.1 | 9.5 | 13.5 | 22.8 | 584.6 | 29.5 |
| Tmax (h) | ||||||||
| Mean | 1.0 | 1.0 | 0.9 | 1.0 | 1.4 | 1.0 | 0.8 | 0.9 |
| SD | 0.1 | 0.2 | 0.2 | 0.2 | 1.3 | 0.1 | 0.5 | 0.2 |
| t1/2 (h) | ||||||||
| Mean | 3.6 | 2.9 | 6.5 | 2.5 | 10.4 | 2.6 | 21.0 | 2.6 |
| SD | 0.7 | 1.1 | 1.3 | 0.7 | 4.8 | 0.6 | 7.2 | 0.3 |
| λz (1/h) | ||||||||
| Mean | 0.2 | 0.3 | 0.1 | 0.3 | 0.1 | 0.3 | 0.0 | 0.3 |
| SD | 0.0 | 0.3 | 0.0 | 0.1 | 0.0 | 0.1 | 0.0 | 0.0 |
| CL (ml/min) | ||||||||
| Mean | 71.2 | 96.7 | 37.8 | 110.3 | 25.7 | 102.3 | 11.7 | 117.2 |
| SD | 13.6 | 19.0 | 9.6 | 19.4 | 10.6 | 20.9 | 4.1 | 28.8 |
| Vz (liters) | ||||||||
| Mean | 22.0 | 23.4 | 20.8 | 23.1 | 20.7 | 21.9 | 19.4 | 25.8 |
| SD | 3.7 | 9.7 | 3.7 | 4.2 | 5.2 | 3.0 | 2.2 | 4.2 |
| Vss (liters) | ||||||||
| Mean | 17.6 | 19.2 | 17.6 | 17.3 | 19.0 | 17.1 | 17.7 | 18.4 |
| SD | 3.1 | 3.5 | 2.8 | 2.0 | 4.7 | 3.6 | 3.3 | 4.0 |
| Rresidence time (h) | ||||||||
| Mean | 4.2 | 3.3 | 8.2 | 2.7 | 13.9 | 2.9 | 27.7 | 2.6 |
| SD | 1.0 | 0.5 | 2.2 | 0.5 | 6.5 | 0.8 | 10.2 | 0.3 |
| ZID | ||||||||
| AUC0–t (h µg/ml) | ||||||||
| Mean | 202.7 | 151.2 | 431.6 | 129.3 | 368.6 | 139.1 | 694.2 | 127.4 |
| SD | 42.0 | 26.8 | 107.5 | 26.0 | 145.8 | 28.7 | 188.5 | 32.1 |
| AUC0–∞ (h µg/ml) | ||||||||
| Mean | 205.1 | 153.2 | 438.5 | 130.9 | 416.6 | 142.5 | 1,184.8 | 129.6 |
| SD | 42.6 | 26.9 | 112.3 | 26.3 | 204.1 | 30.1 | 657.9 | 32.0 |
| Cmax (µg/ml) | ||||||||
| Mean | 55.1 | 54.4 | 57.8 | 49.5 | 29.0 | 53.1 | 219.9 | 48.9 |
| SD | 11.1 | 13.6 | 7.0 | 4.9 | 6.3 | 9.6 | 267.7 | 13.1 |
| Tmax (h) | ||||||||
| Mean | 1.0 | 1.0 | 0.9 | 0.9 | 1.6 | 1.0 | 0.9 | 0.9 |
| SD | 0.1 | 0.2 | 0.2 | 0.2 | 1.2 | 0.1 | 0.8 | 0.2 |
| t1/2 (h) | ||||||||
| Mean | 3.7 | 2.7 | 7.1 | 2.6 | 12.9 | 2.5 | 35.4 | 2.6 |
| SD | 0.8 | 1.1 | 2.2 | 0.8 | 6.5 | 0.6 | 19.0 | 0.4 |
| λz (1/h) | ||||||||
| Mean | 0.2 | 0.3 | 0.1 | 0.3 | 0.1 | 0.3 | 0.0 | 0.3 |
| SD | 0.0 | 0.3 | 0.0 | 0.1 | 0.0 | 0.1 | 0.0 | 0.0 |
| CL (ml/min) | ||||||||
| Mean | 84.3 | 111.9 | 40.3 | 131.5 | 24.4 | 121.5 | 9.0 | 135.8 |
| SD | 17.4 | 22.0 | 10.7 | 25.3 | 11.6 | 26.4 | 4.7 | 36.1 |
| Vz (liters) | ||||||||
| Mean | 26.5 | 26.0 | 23.4 | 28.0 | 23.4 | 25.4 | 21.8 | 29.8 |
| SD | 4.1 | 10.5 | 4.5 | 6.5 | 6.5 | 4.1 | 0.5 | 6.4 |
| Vss (liters) | ||||||||
| Mean | 21.2 | 21.9 | 20.4 | 20.5 | 21.2 | 19.9 | 20.6 | 21.0 |
| SD | 3.8 | 3.6 | 3.5 | 2.7 | 5.2 | 4.3 | 2.4 | 5.1 |
| Residence time (h) | ||||||||
| Mean | 4.3 | 3.3 | 9.0 | 2.7 | 17.4 | 2.8 | 48.7 | 2.6 |
| SD | 1.2 | 0.5 | 3.0 | 0.5 | 9.7 | 0.8 | 27.2 | 0.4 |
a
n = 46. Mean indicates arithmetic mean.
b
Two subjects in the ESRD on HD group were excluded from the plasma PK population due to spuriously high concentrations.