In vitro kinetics of nerve agent degradation by fresh frozen plasma (FFP).
Great efforts have been undertaken in the last decades to develop new oximes to reactivate acetylcholinesterase inhibited by organophosphorus compounds (OP). So far, a broad-spectrum oxime effective against structurally diverse OP is still missing, and alternative approaches, e.g. stoichiometric and catalytic scavengers, are under investigation. Fresh frozen plasma (FFP) has been used in human OP pesticide poisoning which prompted us to investigate the in vitro kinetics of OP nerve agent degradation by FFP. Degradation was rapid and calcium-dependent with the G-type nerve agents tabun, sarin, soman and cyclosarin with half-lives from 5 to 28 min. Substantially longer and calcium-independent degradation half-lives of 23-33 h were determined with the V-type nerve agents CVX, VR and VX. However, at all the tested conditions, the degradation of V-type nerve agents was several-fold faster than spontaneous hydrolysis. Albumin did not accelerate the degradation of nerve agents. In conclusion, the fast degradation of G-type nerve agents by FFP might be a promising tool, but would require transfusion shortly after poisoning. FFP does not seem to be suitable for detoxifying relevant agent concentrations in case of human poisoning by V-type nerve agents.
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, Munich, Germany, TimoWille@bundeswehr.org.
Timo
T
Wille
Horst
H
Thiermann
Franz
F
Worek
D043303:Aryldialkylphosphatase / Q000378:metabolism; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics; D004492:Edetic Acid / Q000494:pharmacology; D005615:Freezing; D006207:Half-Life; D006801:Humans; D008658:Inactivation, Metabolic; D010755:Organophosphates / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics; D010949:Plasma / Q000187:drug effects* / Q000378:metabolism*; D012524:Sarin / Q000493:pharmacokinetics; D012999:Soman / Q000493:pharmacokinetics
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D009943:Organophosphorus Compounds; D001312:Aurintricarboxylic Acid; D012999:Soman; D004492:Edetic Acid; D012524:Sarin; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C009374:tabun; D002118:Calcium; C053914:cyclohexyl methylphosphonofluoridate