Study of the pharmacokinetics of a new sidnonymine derivative in mice with intragastric administration

Relevance. BBP2023 is a new drug candidate of the sydnonimine group, possessing predominantly central vasodilating activity.

Objective. To study the pharmacokinetics of the drug candidate BBP2023 in mice after intragastric administration, including an assessment of distribution to organs and tissues.

Materials and methods. Experiments were performed on 102 outbred male mice. The animals received a single intragastric dose of BBP2023 at 22.0 mg/kg as an oil emulsion. The total duration of the experiment was 72 hours, during which the animals were euthanized by decapitation at specific time points. Plasma was obtained from blood; homogenates were prepared from internal organs (liver, kidneys, heart, lungs, brain, spleen, muscles, omentum). These were analyzed for the quantitative content of BBP2023 and its metabolites using a previously developed and validated HPLC-MS/MS method. The main pharmacokinetic parameters were calculated using a non-compartmental method.

Results. After intragastric administration, BBP2023 was detected in all studied organs and tissues. The time to reach the maximum concentration (0.58 μg/ml) in plasma was 15 minutes, and the elimination half-life was about 7.9 hours. The highest distribution found was to the liver (fr = 2.83), lungs (fr = 1.58), and omentum (fr = 2.62). The minimum value of the elimination rate constant, excluding blood plasma, was observed in brain tissues. The active metabolite BBP2023 A was primarily localized in the kidneys (fr = 16.85) and liver (fr = 4.61). The time to reach the maximum concentration in all organs and tissues ranged from 15 to 45 minutes.

Conclusion. The results of the study established that the sydnonimine group drug candidate BBP2023, as well as its active metabolite (BBP2023 A), are detected in mouse brain tissues, which contributes to the realization of cerebral vasodilating activity.

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