title: HI-6 oxime (an acetylcholinesterase reactivator): blood plasma pharmacokinetics and organ distribution in experimental pigs.
abstract: OBJECTIVE
  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.
authors: Martin
authors: M
authors: Kuneš
authors: Jaroslav
authors: J
authors: Květina
authors: Jan
authors: J
authors: Bureš
authors: Jana Zdárová
authors: JZ
authors: Karasová
authors: Michal
authors: M
authors: Pavlík
authors: Ilja
authors: I
authors: Tachecí
authors: Kamil
authors: K
authors: Musílek
authors: Kamil
authors: K
authors: Kuca
mesh_terms: D000818:Animals; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D034421:Sus scrofa / Q000097:blood / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; C022870:asoxime chloride