Assessment of potential toxic effects of treated Hemofil injection in rats and mice and on the systemic hemodynamics in dogs.
The toxic effects of treated Hemofil (T-AHF) injection were evaluated by 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 VIII/kg did not produce toxic signs. Both species were found to have an LD50 greater than 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, hematology, 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.
D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005169:Factor VIII / Q000633:toxicity*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects
D005169:Factor VIII