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HI-6 oxime (an acetylcholinesterase reactivator): blood plasma pharmacokinetics and organ distribution in experimental pigs
M Kunes, J Kvetina, J Bures, JZ Karasova, M Pavlik, I Tacheci, K Musilek, K Kuca
Jazyk angličtina Země Švédsko
Grantová podpora
NT14270
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
Zdroj
NLK
ROAD: Directory of Open Access Scholarly Resources
od 2012
PubMed
25638385
Knihovny.cz E-zdroje
- MeSH
- oximy aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- pyridinové sloučeniny aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- reaktivátory cholinesterasy aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- Sus scrofa krev metabolismus MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
OBJECTIVES: Oxime HI-6 DMS (dimethanesulfonate) is an asymmetric bis-pyridinium aldoxime and essential acetylcholinesterase (AChE) reactivator. The high effectiveness is due to its wide spectrum of therapeutic activity against different structures of nerve agents. Aim of this study was to compare plasma time profiles and tissue distribution (to delimitation of potential toxicity risks) after its intramuscular (i.m.) and intragastric (i.g.) administration to experimental pigs. METHODS: The study entered female Landrace pigs (Sus scrofa f. domestica), 4-5 months old animals, 29 +/- 3.2 kg of body weight. Before the HI-6 DMS administration (i.m. injection or i.g. using a gastric tube), vena auricularis was cannulated (under general anaesthesia) for collection of blood samples. The tissue distribution study was carried out at expected t-max. Concentrations of HI-6 DMS in blood plasma and other tissue samples were detected by means of HPLC method. RESULTS: Fast absorption after i.m. administration, relatively slow absorption and no even elimination after i.g. administration were found. Tissue distribution showed low accumulation in the liver, but a higher content in the kidneys and high concentrations in the brain and gastrointestinal wall. CONCLUSIONS: Plasma time profiles after i.g. administration has a prolonged pharmacokinetics. Tissue distribution study showed potential side effects to the stomach due to a higher accumulation of HI-6 in this tissue after i.g. administration but not after a standard i.m. administration. Higher content of HI-6 in the kidneys after i.m. administration suggests the main way of the oxime elimination.
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- $a OBJECTIVES: Oxime HI-6 DMS (dimethanesulfonate) is an asymmetric bis-pyridinium aldoxime and essential acetylcholinesterase (AChE) reactivator. The high effectiveness is due to its wide spectrum of therapeutic activity against different structures of nerve agents. Aim of this study was to compare plasma time profiles and tissue distribution (to delimitation of potential toxicity risks) after its intramuscular (i.m.) and intragastric (i.g.) administration to experimental pigs. METHODS: The study entered female Landrace pigs (Sus scrofa f. domestica), 4-5 months old animals, 29 +/- 3.2 kg of body weight. Before the HI-6 DMS administration (i.m. injection or i.g. using a gastric tube), vena auricularis was cannulated (under general anaesthesia) for collection of blood samples. The tissue distribution study was carried out at expected t-max. Concentrations of HI-6 DMS in blood plasma and other tissue samples were detected by means of HPLC method. RESULTS: Fast absorption after i.m. administration, relatively slow absorption and no even elimination after i.g. administration were found. Tissue distribution showed low accumulation in the liver, but a higher content in the kidneys and high concentrations in the brain and gastrointestinal wall. CONCLUSIONS: Plasma time profiles after i.g. administration has a prolonged pharmacokinetics. Tissue distribution study showed potential side effects to the stomach due to a higher accumulation of HI-6 in this tissue after i.g. administration but not after a standard i.m. administration. Higher content of HI-6 in the kidneys after i.m. administration suggests the main way of the oxime elimination.
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