The mechanism of action of the drug PeFagTal®
Salts of monovalent thallium have a high affinity for RNA (guaranteeing the absence of "leakage" of finished particles of the NDDS system), and when they enter the cytoplasm of the cell, they are not excreted by Pg drug resistance proteins, causing a variety of apoptotic reactions. [Galván-Arzate S, Santamaría A. Thallium toxicity // Toxicol Lett. – 1998. – 99(1). – P: 1-13.; Juan Jose RM, Altamirano-Lozano MA. Genetic toxicology of thallium: a review// Drug and Chemical Toxicology. – 2013. – 36(3). – P:369–383].
Here it should be indicated that the created NDDS system with potassium nitrate (TlNO3) contains 18 micrograms / dose taken per day. The therapeutic index of the created NDDS system with TlNO3 is 15000, which is a good indicator for any NDDS.
The lack of resistance of tumor cells to the drug was confirmed by an assessment of the specific activity of the drug on a model of immunodeficient mice with a vaccinated tumor. The drug caused a significantly significant induction of tumor necrosis, see slide 10.
According to the State Standard 12.1.007-76, FS in the intragastric route of administration can be attributed to class 3 (moderately toxic) for mice (from 234.7±17.91 mg/kg to 250.7±21.96 mg/kg), and for rats - to the 2nd class of toxicity (from 55.49±9.71 mg/kg to 63.06± 9.15 mg/kg).
With intragastric administration of GLF, it was not possible to achieve LD50, since the dose of thallium nitrate is 1.08 mg / kg, which is 46 times less than LD50 and, therefore, GLF can be attributed to class 4 toxicity (low-hazard substances).
It is not realistic for GLF to reach a toxic dose.
With oral administration of GLF to rabbits, the drug is not detected in the blood plasma of animals after 90 – 240 minutes, while its concentration drops to an almost undetectable level by 120 minutes after administration. With the intravascular route of administration, the drug is not detected by thallium in the blood plasma of animals after 90 minutes, and according to the bacteriophage RNA, its level borders on background values.
According to the data of the dependence of the concentration of GLF on time in the blood serum of rats with a single oral and intravascular administration at a dose of 77mcg/kg, model values of the main pharmacokinetic parameters were obtained. The analysis of the obtained results indicates a relatively rapid absorption of the drug with oral administration - Tmax is about 15 minutes. Bioavailability relative to intravascular administration (fa) is 32.7%.
Evaluation of the urinary excretion process, after intravenous excretion of the finished drug acting on integrin avß3 for the treatment of breast cancer, indicates that it is excreted in a small amount (1.4% of the administered dose), while up to 1.09% is excreted in the first 2 hours, i.e. eliminated quickly enough.
Absence of immunogenicity