Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning. (1st September 2019)

• Record Type: Journal Article
• Authors: Tekes, K.; Karvaly, G.; Nurulain, S.; Kuca, K.; Musilek, K.; Adeghate, E.; Jung, Y.-S.; Kalász, H.
• Is Part Of: Chemico-biological interactions. Volume 310(2019)
• Publication Date: 2019-09-01
• Subjects: Butyrylcholinesterase -- Pyridinium aldoxime -- HPLC -- Distribution -- K117 -- K127; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.108737
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: K117 and K127 are proven candidates for treatment following a terrorist attack. Pharmacokinetics of K117 and K127 mirrors time dependence of their distribution. Serum level of K117 (a bis-aldoxime) was sometimes lower than that of K127 (a mono-aldoxime).