Pharmacokinetic profile of promising acetylcholinesterase reactivators K027 and K203 in experimental pigs
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28343895
DOI
10.1016/j.toxlet.2017.03.017
PII: S0378-4274(17)30119-4
Knihovny.cz E-zdroje
- Klíčová slova
- Acetylcholinesterase, K027, K203, Nerve agents, Oxime, Pharmacokinetics, Pigs,
- MeSH
- acetylcholinesterasa metabolismus MeSH
- aplikace orální MeSH
- injekce intramuskulární MeSH
- orgánová specificita MeSH
- oximy aplikace a dávkování krev farmakokinetika MeSH
- plocha pod křivkou MeSH
- pyridinové sloučeniny aplikace a dávkování krev farmakokinetika MeSH
- reaktivátory cholinesterázy aplikace a dávkování krev farmakokinetika MeSH
- Sus scrofa MeSH
- tkáňová distribuce MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene MeSH Prohlížeč
- 1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide MeSH Prohlížeč
- acetylcholinesterasa MeSH
- oximy MeSH
- pyridinové sloučeniny MeSH
- reaktivátory cholinesterázy MeSH
Standard treatment of organophosphorus compounds (OPs) poisoning includes administration of an anti-muscarinic (atropine), anticonvulsive (diazepam) and acetylcholinesterase reactivator (oxime). From a wide group of newly synthesized oximes, oxime K027 and oxime K203 seem to be perspective compounds in some specific OPs intoxication. The available in vitro and in vivo preclinical data indicate that both oximes may be considered for potential human use. The main aim of this study was to establish plasmatic concentration curves of both oximes after intramuscular (i.m.) and intragastric (i.g.) application with subsequent pharmacokinetic analysis and study distribution after (i.m.) application on a non-rodent animal model (experimental pigs; 1500mg/animal). According to the results, both oximes had similar Cmax (K027: 106±19μg/mL and K203: 111±8μg/mL) in Tmax 19±5min, respectively, in 22±3min. Bioavailability of oxime K027 calculated as AUCtotal (8389±1024minμg/mL) was halved compared to oxime K203 (16938±795minμg/mL). The highest concentration from peripheral tissues was found in the kidney and lung, but the brain concentrations stay very low, the plasma/brain ratio being approximately 1%. The applied doses were derived from the recommendation where it is possible to use three autoinjectors to save human life. The results provide us with knowledge about the pharmacokinetics and distribution of these new oximes and may help us to better estimate the human pharmacokinetic profile.
Biomedical Research Center University Hospital Hradec Kralove Czech Republic
Department of Military Surgery Faculty of Military Health Sciences Hradec Kralove Czech Republic
Citace poskytuje Crossref.org
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