Table 2.
Pharmacokinetic parametersa,b
| Parameter (units) | Group 1: healthy (n = 6) | Group 2: mild (n = 6) | Group 3: moderate (n = 6) | Group 4: severe (n = 6) |
|---|---|---|---|---|
| AUClast (ng·h/mL) | 732.8 ± 260.0 | 946.9 ± 147.7 | 1,378.6 ± 264.4 | 1,654.6 ± 664.8 |
| AUC∞ (ng·h/mL) | 737.4 ± 260.8 | 967.4 ± 140.2 | 1,384.2 ± 263.2 | 1,708.5 ± 699.0 |
| Cmax (ng/mL) | 144.0 ± 57.8 | 172.1 ± 45.0 | 271.1 ± 30.4 | 228.8 ± 81.8 |
| tmax (h)c | 1.5 (1.0–3.0) | 1.5 (0.5–3.0) | 2.25 (1.0–2.5) | 1.5 (0.5–3.0) |
| Clast (ng/mL) | 0.3 ± 0.1 | 0.8 ± 0.3 | 0.4 ± 0.1 | 1.5 ± 1.1 |
| λz (h−1) | 0.0796 ± 0.0194 | 0.0593 ± 0.0326 | 0.0691 ± 0.0155 | 0.0499 ± 0.0254 |
| CLP/F (L/h) | 29.67 ± 8.86 | 21.05 ± 3.18 | 14.88 ± 2.75 | 16.24 ± 14.20 |
| Vz/F (L) | 382.9 ± 122.10 | 461.7 ± 244.27 | 222.6 ± 55.68 | 351.1 ± 193.42 |
| t½β (h) | 9.26 ± 2.788 | 15.08 ± 7.655 | 10.46 ± 2.340 | 18.38 ± 11.39 |
| CLR (L/h) | 8.72 ± 2.21 | 6.94 ± 0.80 | 5.49 ± 2.08 | 4.03 ± 3.76 |
| (CLP/F)/CLR | 3.40 | 3.03 | 2.71 | 4.03 |
aGroups categorized according to degree of renal impairment
bValues are mean ± standard deviation except where otherwise stated
cValues are median (range)
AUC, area under the plasma concentration–time curve; AUClast, AUC from time zero to time of last measurable plasma concentration; AUC∞, AUC from time zero to infinity; Clast, last measurable plasma concentration; CLP/F, plasma clearance after oral administration; CLR renal clearance; Cmax, maximum plasma concentration; t½β, terminal elimination half-life; tmax, time to reach Cmax; Vz/F, apparent volume of distribution during terminal phase after non-intravenous administration; λz, terminal disposition rate constant