Table 2.
Pharmacokinetic parameters
| 0.005 mg/kg (n = 4) | 0.02 mg/kg (n = 6) | 0.04 mg/kg (n = 6) | 0.08 mg/kg (n = 6) | 0.12 mg/kg (n = 6) | 0.24 mg/kg (n = 6) | 0.48 mg/kg (n = 6) | |
|---|---|---|---|---|---|---|---|
| Plasma | |||||||
| AUC0-25 h*, h*ng/ml | 18.58 ± 3.05 | 78.65 ± 7.96 | 154.50 ± 17.78 | 374.64 ± 37.12 | 470.27 ± 89.88 | 1597.39 ± 267.44 | 3065.25 ± 656.90 |
| AUCinf, h*ng/ml | 18.55 ± 3.00 | 78.63 ± 7.96 | 154.57 ± 17.81 | 375.52 ± 37.65 | 470.79 ± 90.29 | 1600.39 ± 267.48 | 3070.10 ± 657.98 |
| AUClast, h*ng/ml | 18.25 ± 3.05 | 78.04 ± 7.85 | 153.72 ± 17.55 | 374.64 ± 37.12 | 468.95 ± 91.04 | 1597.39 ± 267.44 | 3065.25 ± 656.90 |
| CL, L/h | 12.54 ± 1.63 | 11.36 ± 0.68 | 13.40 ± 1.89 | 10.09 ± 0.78 | 12.46 ± 3.37 | 7.75 ± 1.48 | 8.12 ± 2.48 |
| Cmax, ng/ml | 11.6 ± 1.75 | 42.2 ± 4.11 | 86.6 ± 17.4 | 196 ± 20.3 | 278 ± 42.6 | 855 ± 82.3 | 1970 ± 391 |
| ke, l/h | 0.43 ± 0.04 | 0.32 ± 0.07 | 0.25 ± 0.04 | 0.18 ± 0.03 | 0.24 ± 0.09 | 0.17 ± 0.03 | 0.19 ± 0.02 |
| MRT, h | 1.21 ± 0.12 | 1.70 ± 0.38 | 1.83 ± 0.81 | 1.91 ± 0.16 | 1.54 ± 0.34 | 1.78 ± 0.29 | 1.80 ± 0.24 |
| Tmax, h | 1.0 (1.0–1.0) | 1.0 (1.0–1.0) | 1.0 (1.0–1.0) | 1.0 (1.0–1.0) | 1.0 (1.0–1.0) | 1.0 (0.7–1.0) | 1.0 (1.0–1.0) |
| Vd, L | 29.35 ± 5.67 | 36.70 ± 6.72 | 54.09 ± 12.03 | 57.80 ± 9.04 | 55.98 ± 17.99 | 47.84 ± 15.32 | 44.51 ± 16.22 |
| T1/2, h | 1.61 ± 0.14 | 2.25 ± 0.44 | 2.78 ± 0.41 | 3.97 ± 0.56 | 3.20 ± 0.87 | 4.24 ± 0.75 | 3.75 ± 0.34 |
| Urine | |||||||
| Ae0-25 h#, mg | 0.058 ± 0.015 | 0.311 ± 0.036 | 0.450 ± 0.307 | 1.161 ± 0.353 | 1.621 ± 0.396 | 3.869 ± 1.517 | 6.099 ± 2.424 |
| Ae0-49 h#, mg | 0.058 ± 0.016 | 0.313 ± 0.037 | 0.455 ± 0.308 | 1.170 ± 0.356 | 1.633 ± 0.401 | 3.898 ± 1.530 | 6.150 ± 2.440 |
| CLr, L/h | 3.115 ± 0.572 | 3.957 ± 0.364 | 2.924 ± 1.942 | 3.080 ± 0.809 | 3.493 ± 0.867 | 2.380 ± 0.631 | 1.966 ± 0.545 |
| Fe0-49 h#, % | 25.331 ± 6.394 | 35.235 ± 4.080 | 21.727 ± 14.243 | 30.818 ± 8.068 | 29.245 ± 7.618 | 31.460 ± 9.153 | 25.658 ± 8.754 |
All data were described as “mean ± standard deviation,” except Tmax was described as “median (range)”
Ae amount of drug excreted in urine, AUC area under the curve, CL clearance, Cmax maximal concentration, CLr renal clearance, Fe excreted fraction, ke elimination rate constant, MRT mean residence time, Tmax time to peak drug concentration, T1/2 half-life, Vd distribution volume
*The dose group of 0.005 mg/kg in the pre-phase was AUC0-24 h
#The urine pharmacokinetic parameters of the dose group of 0.005 mg/kg in the pre-phase were Ae0-24 h, Ae0-48 h, and Fe0-48 h