新型神经保护剂——苯并喹喔啉酮衍生物在兔和大鼠体内静脉给药后的药代动力学研究。

Pharmacokinetics of a New Neuroprotector - Indenoquinoxalinone Derivative after Intravenous Administration in Rabbits and Rats.

机构信息

E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.

National Research Tomsk Polytechnic University, Tomsk, Russia.

出版信息

Bull Exp Biol Med. 2023 Oct;175(6):770-773. doi: 10.1007/s10517-023-05943-7. Epub 2023 Nov 21.

DOI:10.1007/s10517-023-05943-7

PMID:37987946

Abstract

The specific JNK inhibitor and NO donor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) demonstrated pronounced neuroprotective properties in an in vivo model of ischemic stroke in rats. The pharmacokinetic behavior of IQ-1 was studied in two animal species (rats, rabbits) after intravenous administration in a dose of 1 mg/kg. IQ-1 concentrations in venous blood plasma were measured by the liquid chromatography-tandem mass spectrometry method. The pharmacokinetics of IQ-1 was adequately described by the two-compartmental model. The calculated C for IQ-1 in rabbit and rat plasma were 2239.83±1229.55 and 1552.50±182.23 ng/ml, respectively. Two animal species are characterized by extensive tissue distribution of IQ-1 (V exceeded the total body water in rabbits and rats by 3.6 and 5.6 times, respectively) and high clearance values (88-94% of hepatic blood flow).

摘要

特异性 JNK 抑制剂和 NO 供体 11H-茚并[1,2-b]喹喔啉-11-酮肟（IQ-1）在大鼠缺血性中风的体内模型中表现出明显的神经保护特性。在静脉注射 1mg/kg 的剂量后，在两种动物（大鼠、兔）中研究了 IQ-1 的药代动力学行为。通过液相色谱-串联质谱法测量静脉血血浆中的 IQ-1 浓度。IQ-1 的药代动力学通过两室模型得到了很好的描述。在兔和大鼠血浆中计算的 IQ-1 的 C 值分别为 2239.83±1229.55 和 1552.50±182.23ng/ml。两种动物均表现出 IQ-1 的广泛组织分布（V 在兔和大鼠中分别超过总体液的 3.6 倍和 5.6 倍）和高清除率值（88-94%的肝血流量）。