Table 2.
Summary of the single- and multiple-dose pharmacokinetic parameters (mean ± SD) of mizoribine in serum (total N = 12, six for once-daily and six for twice-daily dosing, except where noted)
| Parameter | Day 1: 6 mg kg−1 once daily | Day 1: 6 mg kg−1 twice daily |
|---|---|---|
| Cmax (µg ml−1) | 4.1 ± 1.1 | 4.0 ± 1.9 |
| tmax* (h) | 3.0 (2.0–4.0) | 2.0 (2.0–3.0) |
| AUC0–t (µg h−1 ml−1) | 31.3 ± 8.5 | 22.1 ± 11.0 |
| AUC0–∞ (µg h−1 ml−1) | 31.5 ± 8.7 | 25.8 ± 12.1 (N = 5) |
| AUCτ (µg h−1 ml−1) | 31.3 ± 8.6 | 22.1 ± 11.0 |
| kel (l h−1) | 0.3 ± 0.02 | 0.3 ± 0.05 (N = 5) |
| t1/2 (h) | 3.0 ± 0.3 | 3.0 ± 0.7 (N = 5) |
| CL/F (ml h−1 kg−1) | 203 ± 57 | 283 ± 142 (N = 5) |
| Vz/F (ml kg−1) | 883 ± 230 | 1174 ± 546 (N = 5) |
| Parameter | Day 5: 6 mg kg−1 once daily | Day 7: 6 mg kg−1 twice daily |
| Cmax (µg ml−1) | 4.7 ± 0.9 | 4.6 ± 1.6 (N = 5) |
| tmax* (h) | 2.0 (2.0–4.0) | 3.0 (2.0–3.0) (N = 5) |
| AUCτ (µg h−1 ml−1) | 35.5 ± 8.2 | 31.2 ± 11.0 (N = 5) |
| kel (l h−1) | 0.2 ± 0.02 | 0.2 ± 0.04 (N = 5) |
| t1/2 (h) | 3.0 ± 0.3 | 3.1 ± 0.6 (N = 5) |
| CLss/F (ml h−1 kg−1) | 176 ± 34 | 210 ± 65 (N = 5) |
| Accumulation ratio | 1.15 ± 0.14 | 1.42 ± 0.40 (N = 5) |
| Dose linearity | 1.15 ± 0.14 | 1.31 ± 0.41 (N = 5) |
*
Median and range for tmax.