TABLE 6.
PK properties of NDD-713 and -825 in rat after single bolus i.v. or p.o. administration (hydrochloride salt forms)
| Parameter | Dose, i.v. |
|||||
|---|---|---|---|---|---|---|
| 2 mg/kg |
6 mg/kg |
20 mg/kg |
||||
| NDD-713 | NDD-825 | NDD-713 | NDD-825 | NDD-713 | NDD-825 | |
| t1/2, app (h) | 1.7 ± 0.2 | 5.3 ± 0.3 | 1.6 ± 0.1 | 7.3 ± 0.1 | 2.0 ± 0 | 7.1 ± 1.3 |
| Plasma CLtotal (ml/min/kg) | 62 ± 4 | 54 ± 2 | 43 ± 1 | 59 ± 1 | 51 ± 2 | 55 ± 1 |
| Blood CLtotal (ml/min/kg) | 51 ± 3 | 39 ± 1 | 36 ± 1 | 42 ± 1 | 42 ± 1 | 39 ± 1 |
| Vss (L/kg) | 4.3 ± 0.4 | 6.0 ± 0.5 | 3.6 ± 0.2 | 5.0 ± 0 | 4.2 ± 0.2 | 4.7 ± 0 |
| AUC0-t (μM ⋅ h) | 1.2 ± 0.1 | 1.4 ± 0 | 4.6 ± 0.3 | 3.8 ± 0.2 | 14.7 ± 1.0 | 12.1 ± 0.3 |
| AUC0-t/dose [μM ⋅ h/(mg/kg)] | 0.6 ± 0.1 | 0.6 ± 0 | 0.8 ± 0 | 0.6 ± 0 | 0.7 ± 0 | 0.6 ± 0 |
| Dose, p.o. |
||||||
|---|---|---|---|---|---|---|
| Parameter | 2 mg/kg |
10 mg/kg |
20 mg/kg |
|||
| NDD-713 | NDD-825 | NDD-713 | NDD-825 | NDD-713 | NDD-825 | |
| t1/2, app (h) | n.d. | 9.8 ± 0.2 | 1.5 ± 0 | 4.6 ± 0.1 | 2.1 ± 0 | 3.3 ± 0.2 |
| Cmax (μM) | 0.2 ± 0.1 | 0.1 ± 0 | 2.1 ± 0.6 | 0.8 ± 0.1 | 2.0 ± 0.1 | 1.4 ± 0.3 |
| tmax (min) | 30 ± 0 | 83 ± 70 | 45 ± 15 | 45 ± 25 | 45 ± 15 | 186 ± 64 |
| AUC0-t (μM ⋅ h) | 0.6 ± 0.2 | 0.4 ± 0.1 | 5.1 ± 0.2 | 3.0 ± 0.4 | 6.3 ± 0.3 | 11.9 ± 3.0 |
| AUC0-t/dose [μM ⋅ h/(mg/kg)] | 0.4 ± 0.1 | 0.2 ± 0 | 0.5 ± 0.1 | 0.3 ± 0.1 | 0.3 ± 0 | 0.5 ± 0.2 |
| F (%) | 50 ± 11 | 32 ± 5 | 77 ± 3 | 45 ± 6 | 44 ± 1 | 89 ± 24 |
Values shown are means ± sd (n = 3). N.d., not determined.