Study of the pharmacokinetics of a new sidnonymine derivative in rabbits with various routes of administration

Relevance. The search for vasodilating agents that predominantly accumulate in brain tissues is an urgent task. One of the drug candidates with cerebral vasodilating activity is BBP2023 a derivative of sydnonymine. Objective. A comparative assessment of the pharmacokinetics of BBP2023 in rabbits after a single administration via different routes. Methods. Experiments were performed using a crossover design on 8 rabbits. The rabbits received a single dose of BBP2023 at 2.0 mg/kg as an oil emulsion intragastrically and rectally, and as an aqueous DMSO solution intravenously and intramuscularly. Blood samples were collected from the marginal ear vein at specific time points. The quantitative determination of BBP2023 and its metabolites in blood plasma was performed using HPLC-MS/MS. Results. It was found that the highest bioavailability values are achieved with intramuscular administration (97.4 %). With intragastric and rectal administration, this indicator averaged 46.1 and 15.3 %, respectively. The maximum concentration of BBP2023 in blood plasma is reached on average 5 minutes after intragastric administration and averages 0.620 μg/ml; the half-life value averages 1 hour. The maximum concentration of the active metabolite BBP2023 A in blood plasma after intragastric administration is detected on average after 25 minutes and is 0.076 μg/ml. Conclusion. The pharmacokinetics of the active pharmaceutical substance of drug candidate BBP2023 was studied in rabbits. The results obtained were used for the subsequent selection of the optimal finished dosage form and route of administration.