| Abstrakt: |
The toxic effects of treated Hemofil (T-AHF) injection were evaluated fay acute and subchronic intravenous administration to rats, mice, and dogs. Acute iv administration of T-AHF to rats and mice at dosages of 1320 units (U) of Factor Vlll/kg did not produce toxic signs. Both species were found to have an LD50 > 1320 U. Seven-day iv administration to rats of T-AHF at dosages of 20, 40, and 60 U/kg and 3-mo administration (3 times/wk for 13 wk) of T-AHF at dosages of 100 and 200 U/kg did not produce any signs of toxicity. There were no treatment-related effects on body weights, hema-tology, clinical chemistry, urinalysis, ocular tissues, or histopathology. Intravenous administration to dogs at 0.5, 1.0, and 5.0 ml/min ?kg (28 U/ml, 100 U/kg at each rate) produced no significant adverse effects on mean arterial pressure, cardiac output, or heart rate. No adverse changes in pulmonary function, as reflected by arterial blood-gas profiles, were observed. It is concluded that animals tolerated well T-AHF administered at dosages and rates similar to or greater than dosages used clinically. The results obtained from these studies establish a reasonable margin of safety and support the acceptability of the T-AHF for clinical use. |
