ABSTRACT
Pre-clinical toxicologic studies were conducted of a new drug teraphtal-Lio (TPh) and a teraphtal-Lio + ascorbic acid (TPh + AA) catalytic system recommended for binary catalytic therapy of malignant tumors. Quantitative criteria for "acute" and "chronic" toxicity of TPh and TPh + AA were established, which describe their toxic effects in single or multiple application. The coefficient of specific sensitivity and cumulation index for TPh and TPh + AA were determined. The toxicodynamic characteristics of TPh and TPh + AA were investigated. The results were used to prognose pulmonary, cardio-vascular, hemato- and hepatotoxic as well as hemodynamic and ophthalmologic disorders and functional changes in the central nervous system involved in clinical use of TPh and TPh + AA.
Subject(s)
Antineoplastic Agents/toxicity , Indoles/toxicity , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Drug Evaluation, Preclinical , Female , Humans , Indoles/administration & dosage , Indoles/adverse effects , Male , Mice , Prognosis , Rats , Time FactorsABSTRACT
Teraphtal-Lio (Tph) exerted a toxic dose-dependent effect on the hemostatic system. Treatment of experimental animals with maximum tolerated and highly toxic doses was followed by acute DVS syndrome formation involving a hemophilic condition, soaring activated partial prothrombin time, absence of fibrinogen, sharp rise in fibrinogen degradation product and D-dimer matched by fall in thrombocyte count. No toxic influence on the hemostatic system was registered when Tph doses recommended for humans in the course of phase II clinical trials were administered to animals.
