title: Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.
abstract: OBJECTIVE
  Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration.
  
  
  METHODS
  Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight.
  
  
  RESULTS
  The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment.
  
  
  CONCLUSIONS
  I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions.
authors.affiliation: Biomedical Research Center, University Hospital, Hradec Králové, Czech Republic. karasova@pmfhk.cz.
authors.forename: Jana
authors.initials: J
authors.lastname: Zdarova Karasova
authors.affiliation: Departments of Public Health, Toxicology and Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Králové, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Zemek
authors.affiliation: Biomedical Research Center, University Hospital, Hradec Králové, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kunes
authors.affiliation: 2nd Department of Internal Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kvetina
authors.affiliation: Department of Pharmacology, Faculty of Medicine Charles University, Hradec Králové, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Chladek
authors.affiliation: Biomedical Research Center, University Hospital, Hradec Králové, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.affiliation: 2nd Department of Internal Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Bures
authors.affiliation: 2nd Department of Internal Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic.
authors.forename: Ilja
authors.initials: I
authors.lastname: Tachecí
authors.affiliation: Biomedical Research Center, University Hospital, Hradec Králové, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000042:Absorption; D000818:Animals; D001682:Biological Availability; D002712:Chlorides / Q000008:administration & dosage / Q000493:pharmacokinetics; D002801:Cholinesterase Reactivators / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D010091:Oximes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011726:Pyridinium Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D012492:Salts / Q000008:administration & dosage / Q000493:pharmacokinetics; D013451:Sulfonic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D013552:Swine
chemical_list: D002712:Chlorides; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D012492:Salts; D013451:Sulfonic Acids; C022870:asoxime chloride