[Effect of an polyvalent proteinase inhibitor on experimental inflammations].
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Biomedical subjects
Publications and source records attributed to H Ronneberger.
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The specific thrombin inhibitor r-hirudin (HBW 023) has been demonstrated to be effective in preventing thrombosis in preclinical models. Up to now, no bleeding complications have been observed using therapeutically effective doses in animals studies. However, in case of inadvertent overdosing the occurrence of undesired impairment of coagulation cannot be excluded. As a potential antidote an activated prothrombin complex concentrate (APC) was tested on its ability to normalize blood coagulation. APC given s bolus injections 5 min and 3.0 mg/kg neutralized the r-hirudin-induced prolongation and 3.0 mg/kg neutralized the r-hirudin-induced prolongation of whole blood coagulation time in rabbits completely within 5 min without any clot formation in the blood vessels or capillaries of the heart, kidneys, or lungs. Furthermore, bleeding time prolongation induced by bolus application of 3.0 and 30.0 mg/kg r-hirudin was significantly inhibited by APC within 5 min. These results suggest that administration of APC may be an effective way to reverse the effects of r-hirudin in the coagulation system in case of inadvertent overdosing of r-hirudin.
Neuraminidase was submitted to a preclinical toxicological investigation in short--and long--term experiments. The acute toxicity in mice, rats, and guinea pigs is low (LD 50 i.v.: mouse 30,000 units/kg, rat 44,000 units/kg, guinea pig 7,700 units/kg; s.c.: mouse, rat, guinea pig more than 30,000 u/kg). After i.v. injection into dogs, respiration is not at all and blood pressure only slightly altered. Neuraminidase is pyrogenfree in the rabbit test. Assays of antigenicity in guinea pigs and tests on local i.v., i.m., s.c. toxicity in rabbits and guinea pigs showed only moderate toxic signs. Chronicity studies were performed in dogs and rats over 90 days with repeated administration of various amounts of Neuraminidase (dogs 50-2,000 u/kg, rats 500-2,000 u/kg i.v., 26 or 65 injections). Only in very high dose levels (more than 500 u/kg) Neuraminidase was toxic in dogs (damage of liver, kidney and erythrocytes). In lower doses in dogs and in rats the clinical, biochemical, and hematological data as well as urinalysis and anatomopathological results give no evidence of systemic or important alterations which would preclude the clinical investigation of the drug.