title: Investigations of kinetic interactions between lipid emulsions, hydroxyethyl starch or dextran and organophosphorus compounds.
abstract: BACKGROUND
  Numerous studies demonstrated a limited efficacy of clinically used oximes in case of poisoning by various organophosphorus compounds. A broad spectrum oxime antidote covering all organophosphorus nerve agents and pesticides is still missing and effective (bio-)scavengers have not yet been marketed.
  
  
  OBJECTIVE
  The interactions of the available and clinically approved hydroxyethyl starch, dextran and lipid emulsions with organophosphorus nerve agents and pesticides were investigated in order to provide an in vitro base for the evaluation of these compounds in human organophosphorus poisoning.
  
  
  METHODS
  The degradation kinetics of organophosphorus compounds by the glucose derivatives and lipid emulsions were investigated with an acetylcholinesterase inhibition assay.
  
  
  RESULTS
  The incubation of organophosphorus compounds with TRIS-Ca(2+) buffer resulted in a time-dependent degradation of the nerve agents with half-lives of 42 min for cyclosarin, 49 min for sarin, 99 min for tabun, 107 min for soman 19 h for malaoxon and 54 h for VX. In contrast, incubation with all tested compounds resulted in a stabilisation of the organophosphorus compounds.
  
  
  CONCLUSIONS
  Our results suggest that binding of lipophilic organophosphorus compounds could result in a reduced spontaneous and enzyme-induced degradation of the toxic compounds.
  
  
  CONCLUSIONS
  High dose lipid emulsions and glucose derivatives stabilised organophosphorus compounds in vitro.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.
authors.forename: J
authors.initials: J
authors.lastname: Von Der Wellen
authors.forename: F
authors.initials: F
authors.lastname: Worek
authors.forename: H
authors.initials: H
authors.lastname: Thiermann
authors.forename: T
authors.initials: T
authors.lastname: Wille
mesh_terms: D001673:Biodegradation, Environmental; D002619:Chemical Warfare Agents / Q000737:chemistry / Q000506:poisoning; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology; D004655:Emulsions / Q000737:chemistry*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008294:Malathion / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity; D062025:Organophosphate Poisoning / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D010755:Organophosphates / Q000737:chemistry* / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000633:toxicity; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D003911:Dextrans; D004655:Emulsions; D006895:Hydroxyethyl Starch Derivatives; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010575:Pesticides; C100082:malaoxon; C009374:tabun; D008294:Malathion; C053914:cyclohexyl methylphosphonofluoridate