Table 5.
Pharmacokinetic parameters for CHF 4227 after administration of repeated oral doses. Data are shown as mean ± SEM
| CHF 4227 dose | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 5 mg | 10 mg | 25 mg | 50 mg | 100 mg | ||||||
| Day 1 | Day 28 | Day 1 | Day 28 | Day 1 | Day 28 | Day 1 | Day 28 | Day 1 | Day 28 | |
| Cmax (ng ml−1) | 0.25 ± 0.031 | 1.16 ± 0.28 | 0.76 ± 0.12 | 2.59 ± 0.42 | 1.76 ± 0.35 | 5.37 ± 3.23 | 2.58 ± 0.39 | 9.02 ± 1.75 | 7.37 ± 1.79 | 22.97 ± 5.93 |
| tmax (h)# | 6.0 | 4.0 | 12.0 | 6.0 | 8.0 | 4.0 | 6.0 | 6.0 | 6.0 | 6.0 |
| (3.0–24.0) | (0–6.0) | (3.0–24.0) | (2.0–8.0) | (3.0–12.0) | (0–6.0) | (2.0–12.0) | (1.0–8.0) | (4.0–6.0) | (3.0–6.0) | |
| t1/2 (h) | – | 52.3 | – | 51.8 | – | 53.2 | – | 35.4 | – | 47.0 |
| AUC(0,24 h) (ng ml−1 h) | 4.4 ± 0.6 | 22.9 ± 6.2 | 13.0 ± 2.1 | 47.6 ± 7.5 | 25.4 ± 4.1 | 97.3 ± 19.9 | 18.3 ± 3.1 | 140.6 ± 28.6 | 55.1 ± 11.7 | 429.6 ± 130.0 |
| Rac | – | 5.04 | – | 3.26 | – | 3.9 | – | 9.83 | – | 7.28 |
| PTF (%) | 52.1 | 61.8 | 65.8 | 98.6 | 65.8 | |||||
#
Median and range on day 28; AUC(0,24 h) stands for AUCss.