K117 和 K127 的药代动力学研究，两种新型抗沙林毒剂解毒剂候选药物。
Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning.
机构信息
Department of Pharmacodynamics, Semmelweis University, H-1089, Budapest, Nagyvárad tér 4, Hungary.
Department of Laboratory Medicine, Semmelweis University, H-1089, Budapest, Nagyvárad tér 4, Hungary.
出版信息
Chem Biol Interact. 2019 Sep 1;310:108737. doi: 10.1016/j.cbi.2019.108737. Epub 2019 Jul 4.
AIMS
K117 and K127 are bis-pyridinium aldoximes but K117 is a bis-pyridinium bis-aldoxime while K127 has only one single aldoxime in addition to its amide substituent. Is there any difference in pharmacokinetics in these compounds that otherwise have the same chemical structure? Both K117 and K127 are developed as antidotes in acetylcholinesterase and butyrylcholinesterase poisoning in terrorist attacks or intoxication with other organophosphorous compounds. Their distributions have been scouted in the bodies of rats.
MAIN METHODS
White male Wistar rats were intramuscularly injected. The animals were sacrificed, tissue samples were homogenized, and either K117 or K127 concentrations were determined using reversed-phase high-performance liquid chromatography.
KEY FINDINGS
Both K117 and K127 were present in all tissues that were analyzed including blood (serum), the brains, cerebrospinal fluid, the eyes, livers, kidneys, lungs and testes. Their pharmacokinetics and body distributions are similar.
SIGNIFICANCE
Either K117 or K127 meets the essential requirements for antidotes. Dose dependence and kinetics of their distribution were compared to that of other pyridinium aldoximes.
目的
K117 和 K127 均为双吡啶醛肟，但 K117 是双吡啶双醛肟，而 K127 除了酰胺取代基外，只有一个单醛肟。这些化合物在药代动力学方面是否存在差异，而其他方面的化学结构相同？K117 和 K127 均被开发为在恐怖袭击或其他有机磷化合物中毒中用于乙酰胆碱酯酶和丁酰胆碱酯酶中毒的解毒剂。已经在大鼠体内探测到它们的分布。
主要方法
雄性 Wistar 大鼠肌肉内注射。处死动物，组织样品匀浆，使用反相高效液相色谱法测定 K117 或 K127 的浓度。
主要发现
K117 和 K127 均存在于所有分析的组织中，包括血液（血清）、大脑、脑脊液、眼睛、肝脏、肾脏、肺和睾丸。它们的药代动力学和体内分布相似。
意义
K117 或 K127 均符合解毒剂的基本要求。比较了它们的分布与其他吡啶醛肟的剂量依赖性和动力学。
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