Parameter (unit) | Dose level (mg/kg) | |||||||
---|---|---|---|---|---|---|---|---|
0.5 (n = 6) | 1 (n = 6) | 2 (n = 6) | 3.5 (n = 9) | 6 (n = 12) | 10 (n = 9) | 13 (n = 6) | ||
C max (μg/mL) | Mean | 3.32 | 10.3 | 23.1 | 51.7 | 118 | 194 | 259 |
Min-max | 2.31-4.85 | 6.06-14.1 | 16.0-31.1 | 37.7-68.7 | 59.5-266 | 130-279 | 167-371 | |
CV | 28.5% | 29.8% | 25.4% | 20.8% | 47.3% | 23.2% | 29.7% | |
C 5min (μg/mL) | Mean | 2.58 | 9.26 | 23.6** | 50.2 | 112 | 193 | 248 |
Min-max | 1.59-3.92 | 5.98-12.5 | 16.7-26.8 | 37.1-68.7 | 51.6-266 | 120-279 | 148-371 | |
CV | 32.0% | 26.7% | 17.7% | 22.9% | 52.3% | 24.3% | 31.6% | |
AUC (0-∞) (μg.h/mL) | Mean | 15.5* | 34.5 | 68.6 | 109 | 229*** | 408 | 651 |
Min-max | 9.13-20.9 | 21.0-43.0 | 50.7-81.5 | 81.0-163 | 147-307 | 303-501 | 468-814 | |
CV | 35.0% | 21.8% | 17.1% | 23.6% | 21.8% | 18.8% | 21.4% | |
Terminal t 1/2 (h) | Mean | 29.5 | 25.1 | 26.4 | 25.1 | 24.4 | 25.3 | 24.4 |
Min-max | 27.0-31.5 | 22.9-26.8 | 24.3-28.7 | 23.1-27.7 | 21.2-30.0 | 19.3-30.2 | 20.1-28.6 | |
CV | 6.3% | 5.6% | 6.2% | 7.0% | 11.1% | 12.8% | 12.4% | |
CL (mL/min/kg) | Mean | 0.598 | 0.509 | 0.499 | 0.560 | 0.460 | 0.422 | 0.347 |
Min-max | 0.399-0.912 | 0.388-0.792 | 0.409-0.657 | 0.357-0.721 | 0.326-0.680 | 0.332-0.549 | 0.266-0.463 | |
CV | 39.3% | 28.6% | 18.7% | 20.9% | 25.3% | 20.0% | 22.7% | |
V z (mL/kg) | Mean | 1.54 | 1.11 | 1.14 | 1.22 | 0.964 | 0.929 | 0.723 |
Min-max | 1.03-2.49 | 0.899-1.77 | 0.910-1.52 | 0.723-1.52 | 0.611-1.34 | 0.624-1.44 | 0.599-0.989 | |
CV | 43.4% | 30.5% | 19.7% | 20.5% | 23.5% | 26.8% | 20.0% |