Table I.
Non-compartmental Model-Based Pharmacokinetic Parameters of AR and Its Metabolites After Intravenous (IV) and Oral AR Administrations in Rats (n = 6 per Treatment Group, Results Were Presented as Mean ± SD)
| Route | Analyte | Dose (μmol) | K e (1/min) | T 1/2 (min) | T max (min) | C max (μmol/L) | AUC0–∞ (min μmol/L) | V/V_F (L) | Cl/Cl_F (L/min) | AUMC (min min μmol/L) | MRT (min) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| IV | AR | 0.32 | 0.08 ± 0.02 | 9.35 ± 2.15 | 2.38 ± 1.07 | 0.74 ± 0.23 | 9.32 ± 2.80 | 0.46 ± 0.11 | 0.04 ± 0.02 | 98.5 ± 39.4 | 10.3 ± 1.8 |
| 0.64 | 0.05 ± 0.01 | 13.4 ± 2.2 | 2.00 ± 0.00 | 1.45 ± 0.33 | 19.4 ± 2.9 | 0.65 ± 0.09 | 0.03 ± 0.00 | 278 ± 33 | 14.4 ± 1.0 | ||
| 1.61 | 0.05 ± 0.01 | 13.0 ± 1.8 | 2.00 ± 0.01 | 4.57 ± 0.69 | 54.1 ± 8.1 | 0.57 ± 0.13 | 0.03 ± 0.01 | 660 ± 126 | 12.1 ± 1.2 | ||
| AG | – | 0.05 ± 0.01 | 14.9 ± 2.1 | 2.38 ± 1.07 | 0.09 ± 0.03 | 1.69 ± 0.52 | 29.7 ± 8.3 | 18.6 ± 6.3 | |||
| – | 0.04 ± 0.00 | 15.6 ± 1.0 | 2.00 ± 0.00 | 0.18 ± 0.05 | 4.38 ± 0.88 | 113 ± 33 | 25.6 ± 2.3 | ||||
| – | 0.05 ± 0.01 | 15.0 ± 2.2 | 4.17 ± 5.30 | 0.39 ± 0.10 | 9.32 ± 1.21 | 235 ± 49 | 25.0 ± 3.0 | ||||
| AA | – | 0.04 ± 0.01 | 17.9 ± 4.1 | 6.13 ± 5.76 | 0.30 ± 0.19 | 7.06 ± 3.60 | 127 ± 75 | 17.6 ± 3.0 | |||
| – | 0.04 ± 0.00 | 19.8 ± 2.2 | 6.17 ± 3.21 | 0.56 ± 0.11 | 16.9 ± 3.0 | 409 ± 65 | 24.4 ± 1.7 | ||||
| – | 0.04 ± 0.01 | 19.5 ± 3.3 | 5.33 ± 2.56 | 1.51 ± 0.35 | 45.3 ± 6.8 | 1,082 ± 162 | 24.0 ± 1.4 | ||||
| Oral | AR | 1.61 | – | – | – | – | – | – | – | – | – |
| 3.22 | – | – | – | – | – | – | – | – | – | ||
| 8.06 | – | – | – | – | – | – | – | – | – | ||
| AA | – | 0.004 ± 0.001 | 196 ± 49 | 15.0 ± 0.0 | 0.01 ± 0.00 | 1.81 ± 0.58 | – | – | 14.4 ± 8.2 | 385 ± 158 | |
| – | 0.004 ± 0.001 | 176 ± 40 | 30.0 ± 16.5 | 0.03 ± 0.02 | 3.63 ± 1.27 | – | – | 10.8 ± 6.2 | 177 ± 51 | ||
| – | 0.004 ± 0.001 | 182 ± 27 | 17.5 ± 6.1 | 0.10 ± 0.03 | 12.3 ± 4.2 | – | – | 32.4 ± 16.2 | 154 ± 49 | ||
| AG | – | 0.001 ± 0.001 | 547 ± 175 | 57.5 ± 25.9 | 0.02 ± 0.01 | 5.42 ± 1.4 | – | – | 42.6 ± 16.6 | 437 ± 105 | |
| – | 0.003 ± 0.001 | 250 ± 70 | 67.5 ± 43.2 | 0.04 ± 0.04 | 5.39 ± 2.8 | – | – | 21.4 ± 9.6 | 268 ± 115 | ||
| – | 0.002 ± 0.000 | 307 ± 61 | 40.2 ± 12.5 | 0.08 ± 0.04 | 13.2 ± 8.2 | – | – | 59.4 ± 45.7 | 259 ± 52 |
K e elimination rate constant, T 1/2 half time, T max time of maximum concentration, C max maximum concentration, AUC 0–∞ area under the concentration curve from time zero to infinity, V/V_F volume of distribution, Cl/Cl_F clearance, AUMC area under the first moment curve, MRT mean residence time, “–” not available