TABLE 4.
PK parameters of brensocatib in Sprague Dawley and Wistar rats during the first 24 h of BID or QD dosing.
| BID | QD | ||||||
|---|---|---|---|---|---|---|---|
| SD | Dose (mg/kg/day) | 0.2 | 2 | 20 | 0.3 | 3 | 30 |
| AUC0–24h (ng•h/mL) | 124 ± 81 | 4728 ± 421 | 72,568 ± 3401 | 269 ± 128 | 11,098 ± 107 | 104,278 ± 25,039 | |
| AUC(0–24) (µmol•h/L) | 0.29 ± 0.19 | 11.24 ± 1.00 | 172.57 ± 8.09 | 0.64 ± 0.30 | 26.39 ± 0.25 | 247.99 ± 59.54 | |
| t1/2 (h), AM dose | n/a | 13.49 ± 9.16 | 14.10 ± 1.55 | 5.36 ± 2.38 | 4.46 ± 0.37 | 3.88 ± 0.04 | |
| t1/2 (h), PM dose | 0.55 ± 0.02 | 7.42 ± 1.16 | 4.03 ± 0.44 | n/a | n/a | n/a | |
| Wistar | Dose (mg/kg/day) | 0.2 | 2 | 20 | 0.3 | 3 | 30 |
| AUC0–24h (ng•h/mL) | 377 ± 78 | 9817 ± 1815 | 173,277 ± 37,673 | 1036 ± 291 | 11,720 ± 2327 | 266,484 ± 22,039 | |
| AUC(0–24) (µmol•h/L) | 0.90 ± 0.18 | 23.35 ± 4.32 | 412.07 ± 89.59 | 2.46 ± 0.69 | 27.87 ± 5.53 | 633.73 ± 52.41 | |
| t1/2 (h), AM dose | 5.48 ± 1.76 | 10.16 ± 1.47 | 7.81 ± 1.38 | 34.31 ± 20.32 | 5.14 ± 0.50 | 4.41 ± 0.18 | |
| t1/2 (h), PM dose | 6.45 ± 0.55 | 4.99 ± 0.33 | 4.33 ± 0.16 | n/a | n/a | n/a | |
AUC, area under the concentration-time curve; t1/2 = half life. Data are presented as mean ± SEM (n = 4, except for SD, 0.2 mg/kg/day AUC, where n = 2 due to confirmed PK, outliers by Grubbs test; SD, 2 mg/kg/day AM t1/2 where n = 2 due to inability to calculate parameter, SD, 2 mg/kg/day AM t1/2 where n = 3 due to confirmed outlier by Grubbs test, SD, 0.3 mg/kg/day AUC, where n = 3 due to confirmed PK, outlier by Grubbs test; SD, 3 mg/kg/day AUC, where n = 2 due to confirmed PK, outliers by Grubbs test; SD, 0.3 mg/kg/day AM t1/2 where n = 3 due to confirmed outlier by Grubbs test, and Wistar 0.2 mg/kg/day where n = 3 due to confirmed PK, outliner by Grubbs test). n/a, not applicable or could not be calculated.