PK parameters of MTX and 7OH MTX
PK parameters are presented as the mean ± S.D. (n = 5). The raw data were log-transformed and the significant difference analysis was done on the transformed data.
| PK Parameter | MTX | 7OH MTX | ||||||
|---|---|---|---|---|---|---|---|---|
| Control | LEF | LEF + HET0016 | LEF + GW6471 | Control | LEF | LEF + HET0016 | LEF + GW6471 | |
| t1/2 (h) | 1.49 ± 0.66 | 0.89 ± 0.13 | 0.77 ± 0.08 | 0.77 ± 0.11 | 2.50 ± 0.53 | 1.57 ± 0.41 | 1.97 ± 1.02 | 1.91 ± 0.74 |
| Tmax (h) | NA | NA | NA | NA | 0.25 ± 0.17 | 0.50 ± 0.00 | 0.60 ± 0.22 | 0.50 ± 0.00 |
| Cmax (μg/ml) | NA | NA | NA | NA | 0.384 ± 0.080 | 1.721 ± 0.343*** | 1.479 ± 0.948** | 0.972 ± 0.411 |
| AUC (μg/ml*h) | 7.50 ± 3.30 | 16.2 ± 2.6* | 15.9 ± 7.3* | 8.52 ± 1.52 | 0.576 ± 0.055 | 2.488 ± 0.407*** | 2.765 ± 2.158*** | 1.274 ± 0.333 |
| CL (l/h per kilogram) | 7.48 ± 3.04 | 3.11 ± 0.59** | 3.53 ± 4.27 | 4.62 ± 5.61 | NA | NA | NA | NA |
| MRT0–t (h) | 0.46 ± 0.13 | 0.62 ± 0.02 | 0.59 ± 0.12 | 0.61 ± 0.02 | 1.67 ± 0.19 | 1.49 ± 0.25 | 1.68 ± 0.29 | 1.45 ± 0.36 |
See the illustration in Fig. 7 for details. CL, clearance; MRT0–t, mean residence time from time zero extrapolated until the end of the dosing interval; NA, not applicable; t1/2, elimination half-life; Tmax, time to reach Cmax.
↵* P < 0.05; **P < 0.01; ***P < 0.001 (differences between four groups were analyzed using one-way analysis of variance).