Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning
Language English Country Ireland Media print-electronic
Document type Journal Article
PubMed
31279792
DOI
10.1016/j.cbi.2019.108737
PII: S0009-2797(19)30353-9
Knihovny.cz E-resources
- Keywords
- Butyrylcholinesterase, Distribution, HPLC, K117, K127, Pyridinium aldoxime,
- MeSH
- Acetylcholinesterase chemistry MeSH
- Antidotes pharmacokinetics MeSH
- Butyrylcholinesterase chemistry MeSH
- Chemical Warfare Agents pharmacokinetics MeSH
- Cholinesterase Inhibitors pharmacokinetics MeSH
- Rats MeSH
- Organophosphates antagonists & inhibitors MeSH
- Oximes analysis pharmacokinetics MeSH
- Rats, Wistar MeSH
- Pyridinium Compounds analysis pharmacokinetics MeSH
- Cholinesterase Reactivators pharmacokinetics MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Antidotes MeSH
- Butyrylcholinesterase MeSH
- Chemical Warfare Agents MeSH
- Cholinesterase Inhibitors MeSH
- K117 compound MeSH Browser
- K127 compound MeSH Browser
- Organophosphates MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- tabun MeSH Browser
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.
Department of Anatomy United Arab Emirates University Al Ain United Arab Emirates
Department of Laboratory Medicine Semmelweis University H 1089 Budapest Nagyvárad tér 4 Hungary
Department of Pharmacodynamics Semmelweis University H 1089 Budapest Nagyvárad tér 4 Hungary
Medicinal Science Division Korea Research Institute of Chemical Technology Daejeon Republic of Korea
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