Table 2.
Pharmacokinetic parameters of tofacitinib after oral administration of the drug at various doses to male Sprague-Dawley rats.
| Parameters | 10 mg/kg | 20 mg/kg | 50 mg/kg | 100 mg/kg |
|---|---|---|---|---|
| (n = 7) | (n = 8) | (n = 9) | (n = 7) | |
| Body weight (g) | 312 ± 19.8 | 308 ± 24.5 | 284 ± 22.3 | 286 ± 17.7 |
| AUC (μg∙min/mL) a | 99.4 ± 35.5 | 269 ± 53.7 | 1192 ± 280 | 4073 ± 1787 |
| Dose-normalized AUC (μg∙min/mL) a | 99.4 ± 35.5 | 135 ± 26.9 | 238 ± 56.0 | 407 ± 179 |
| Cmax (μg/mL) | 1.13 ± 0.774 | 3.13 ± 1.27 | 5.62 ± 2.18 | 13.1 ± 5.48 |
| Tmax (min) b | 15.7 ± 7.32 | 15.7 ± 15.9 | 34.4 ± 26.7 | 170 ± 192 |
| CLR (mL/min/kg) c | 11.6 ± 2.87 | 6.97 ± 3.95 | 7.61 ± 2.82 | 3.37 ± 2.52 |
| Ae0–24 h (% of dose) | 11.3 ± 4.60 | 10.0 ± 6.51 | 17.2 ± 3.98 | 13.0± 9.47 |
| GI24 h (% of dose) | 3.16 ± 5.12 | 3.13 ± 3.27 | 2.77 ± 3.96 | 0.772± 0.905 |
| F (%) | 29.1 | 39.3 | 69.7 | 119 |
Data are expressed as mean ± standard deviation (SD). AUC and Cmax values were normalized to tofacitinib dose of 10 mg/kg for statistical analysis. F was calculated by dose-normalized AUC (based on 10 mg/kg) after oral administration of tofacitinib divided by AUC after intravenous administration of the drug at dose of 10 mg/kg. a 10 mg/kg was significantly different (p < 0.05) from 50 mg/kg. 100 mg/kg was significantly different from 10 (p < 0.001), 20 (p < 0.001) and 50 (p < 0.01) mg/kg, respectively. b 100 mg/kg was significantly different (p < 0.05) from 10, 20 and 50 mg/kg. c 10 mg/kg was significantly different from 20 (p < 0.05) and 100 (p < 0.001) mg/kg, respectively.