Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning

K. Tekes, G. Karvaly, S. Nurulain, K. Kuca, K. Musilek, E. Adeghate, Y. S. Jung, H. Kalász

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number108737
JournalChemico-Biological Interactions
Volume310
DOIs
Publication statusPublished - Sep 1 2019

Fingerprint

Antidotes
Pharmacokinetics
Oximes
Poisoning
Rats
Tissue
Cerebrospinal fluid
Butyrylcholinesterase
High performance liquid chromatography
Reverse-Phase Chromatography
Acetylcholinesterase
Amides
Liver
Cerebrospinal Fluid
Testis
Wistar Rats
Brain
Animals
Blood
High Pressure Liquid Chromatography

Keywords

  • Butyrylcholinesterase
  • Distribution
  • HPLC
  • K117
  • K127
  • Pyridinium aldoxime

ASJC Scopus subject areas

  • Toxicology

Cite this

Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning. / Tekes, K.; Karvaly, G.; Nurulain, S.; Kuca, K.; Musilek, K.; Adeghate, E.; Jung, Y. S.; Kalász, H.

In: Chemico-Biological Interactions, Vol. 310, 108737, 01.09.2019.

Research output: Contribution to journalArticle

Tekes, K. ; Karvaly, G. ; Nurulain, S. ; Kuca, K. ; Musilek, K. ; Adeghate, E. ; Jung, Y. S. ; Kalász, H. / Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning. In: Chemico-Biological Interactions. 2019 ; Vol. 310.
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