Table I.
Pharmacokinetic parameters after i.v. administration of NN1731 or rFVIIa to normal dogs.
| Treatment | Assay | Tmax (h) | AUC (h µg/ml) | Cmax (µg/ml) | t½* (h) | Cl (ml/h per kg) | Vss (ml/kg) |
|---|---|---|---|---|---|---|---|
| rFVIIa | FVII EIA | 9·4 ± 0·9 | 3·0 ± 0·5 | 1·9 ± 0·2 | 29 ± 3 | 110 ± 12 | |
| rFVIIa + heparin | FVII EIA | 8·1 ± 0· 5 | 2·3 ± 0·1 | 1·7 ± 0·7 | 34 ± 2 | 140 ± 2 | |
| NN1731 | FVII EIA | 6·5 ± 0· 7 | 2·9 ± 0·4 | 1·6 ± 0·2 | 42 ± 5 | 127 ± 17 | |
| NN1731 + heparin | FVII EIA | 6·5 ± 0· 7 | 2·7 ± 0·2 | 1·8 ± 0·1 | 42 ± 5 | 131 ± 20 | |
| rFVIIa | FVIIa-AT EIA | 2·3 ± 1·0 | 5·1 ± 2· 0 | 0·8 ± 0·4 | 2·1 ± 0·04 | – | – |
| rFVIIa + heparin | FVIIa-AT EIA | 1·5 ± 0·7 | 5·3 ± 0· 7 | 0·8 ± 0·1 | 2·0 ± 0·1 | – | – |
| NN1731 | FVIIa-AT EIA | 0·8 ± 0·2 | 3·2 ± 0· 6 | 0·8 ± 0·1 | 2·7 ± 0·6 | – | – |
| NN1731 + heparin | FVIIa-AT EIA | 0·4 ± 0·2 | 6·3 ± 0·3 | 2·0 ± 0·1 | 2·9 ± 0·1 | – | – |
| rFVIIa | FVIIa clot | 4·1 ± 0· 5 | 2·5 ± 0·5 | 1·1 ± 0·1 | 67 ± 8 | 120 ± 14 | |
| rFVIIa + heparin | FVIIa clot | 3·5 ± 0· 2 | 2·4 ± 0·3 | 0·8 ± 0·3 | 76 ± 4 | 150 ± 20 | |
| NN1731 | FVIIa clot | 16 ± 2·7 | 26 ± 3·6 | 0·5 ± 0·1 | 201 ± 37 | 205 ± 27 | |
| NN1731 + heparin | FVIIa clot | 9·2 ± 0· 1 | 17 ± 0·2 | 0·6 ± 0·1 | 345 ± 3 | 540 ± 64 |
Tmax, time to reach peak concentration; AUC, area under the curve; Cmax, peak concentration; t½, half-life; Cl, clearance; Vss, steady-state volume of distribution.
*
Determined from data in the interval 0–4 h.