Pharmacokinetics of RAS GTpase peptide inhibitor INH-RAS

Objective: to study of the pharmacokinetics of a drug based on a peptide inhibitor of Ras-GTPase (Ing-Ras) Materials and methods. Thirty-six male Sprague-Dawley (SD) rats and 12 male California rabbits were used in the experiment. The experimental drug was administered to animals in two doses of 15 mg/kg and 50 mg/kg once intravenously: rats - in the tail vein in the volume of 2 ml/kg, rabbits - in the ear vein in the volume of 1.5 ml/kg. Blood samples were taken 1, 3, 5, 10, 20, 30,60, 120, 240, 480 minutes after drug administration.ResultsThe concentration of the drug “Ing-Ras” in the blood plasma of rats after 1 minute is about 180 μg/ml (184±12) at a dose of 15 mg/kg and 460 μg/ml (462±28) at a dose of 50 mg/kg. The decrease in concentration is characterized by its half-life of about 4-5 minutes (4.58 minutes at a dose of 15mg/kg, 4.18 minutes at a dose of 50 mg/kg). The mean residence time (MRT) of the drug is about 5 minutes. The steady-state volume of distribution (Vss) is about 90-100 ml/kg (89.7 ml/kg at a dose of 15 mg/kg, 102.8 ml/kg at a dose of 50 mg/kg).The concentration of the drug “Ing-Ras” in the blood plasma of rabbits after 1 minute is about 160 μg/ml (159±10) at a dose of 15 mg/kg and 590 μg/ml (589±15) at a dose of 50 mg/kg. The decrease in concentration is characterized by its half-life of about 4-5 minutes (5.25 minutes at a dose of 15 mg/kg, 4.63 minutes at a dose of 50 mg/kg). The mean residence time (MRT) of the drug is about 6 minutes. The steady-state volume of distribution (Vss) is about 80-85 ml/kg (83.0 ml/kg at a dose of 15 mg/kg, 84.5 ml/kg at a dose of 50 mg/kg).Conclusion. Based on the studies conducted, it was shown that the concentration of the developed peptide inhibitor of Ras-GTPase (“Ing-Ras”) decreases with a half-life of about 4-5 minutes (4.58 minutes with a dose of 15 mg/kg and 4.18 minutes with a dose of 50 mg/kg) in rats and (5.25 minutes with a dose of 15 mg/kg and 4.63 minutes with a dose of 50 mg/kg) in rabbits.