Pharmacokinetics of an antiplatelet drug of indolinone series in the bloodstream

Abstract

The aim of the work is to study the pharmacokinetic profile of the antiplatelet drug of indolinone series (GRS) in the blood plasma of rats and rabbits. GRS was administered once to rats and repeatedly to rabbits intragastrically as a suspension in 0.5% aqueous solution of carboxymethyl cellulose. The study of the predictability of systemic exposure growth in response to dose increase was carried out as part of a study of the linearity of pharmacokinetics in doses of 10, 20 and 40 mg/kg in rats. To assess the absolute bioavailability GRS was injected into the vein in rats at a dose of 1 mg/kg as a solution in 50% polyethylene glycol — 400. Blood from rats after administration was taken at points of 10, 20, 30, 45 min, 1, 2, 4, 8 and 24 h (5 rats per point). To study the possible accumulation of rabbits GRS was orally repeatedly (1 time per day for 10 days) administered, blood was taken after 1, 5 and 10 administration at points of 30, 45 min, 1, 2, 4, 8 and 24 h.

It was found that GRS is rapidly absorbed from the gastrointestinal tract with a maximum concentration at 1 h and has an absolute bioavailability of 23%. The value of the system AUC exposure increases linearly with increasing doses from 10 to 20 mg/kg, increasing the dose to 40 mg/kg does not lead to a corresponding increase in AUC, which goes to the plateau. Repeated (10-fold) intragastric administration of GRS to rabbits does not lead to a significant change in the value of the system exposure.