title: Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds.
abstract: OBJECTIVE
  Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level in the range of 10-20 microM was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients.
  
  
  METHODS
  After admission to the intensive care unit (ICU) the obidoxime regimen (250 mg i.v. as bolus, followed by 750 mg/24h) was started and maintained as long as reactivation was possible. Plasma concentrations of obidoxime were determined by HPLC.
  
  
  RESULTS
  A total amount of 2269+/-1726 mg obidoxime was infused over 65 h+/-55 h resulting in a steady state plasma concentration of 14.5+/-7.3 microM. Obidoxime was eliminated with t(1/2(1)) 2.2 and t(1/2(2)) 14 h. The volumes of distribution amounted to 0.32+/-0.1L/kg (V((1))) and 0.28+/-0.12 (V((2)))L/kg. Postmortem examination of tissue in one patient showed obidoxime accumulation in cartilage, kidney and liver and pointed to brain concentrations similar to plasma concentration.
  
  
  CONCLUSIONS
  Using the suggested obidoxime regimen, the targeted plasma concentration could be achieved. Obidoxime was eliminated biphasically and was well tolerated. This result allows the recommendation of using this definite regimen for adults also in case of mass casualties.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany. HorstThiermann@bundeswehr.org
authors.forename: H
authors.initials: H
authors.lastname: Thiermann
authors.forename: F
authors.initials: F
authors.lastname: Eyer
authors.forename: N
authors.initials: N
authors.lastname: Felgenhauer
authors.forename: R
authors.initials: R
authors.lastname: Pfab
authors.forename: T
authors.initials: T
authors.lastname: Zilker
authors.forename: P
authors.initials: P
authors.lastname: Eyer
authors.forename: F
authors.initials: F
authors.lastname: Worek
mesh_terms: D000328:Adult; D000368:Aged; D002801:Cholinesterase Reactivators / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009768:Obidoxime Chloride / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D062025:Organophosphate Poisoning; D055815:Young Adult
chemical_list: D002801:Cholinesterase Reactivators; D009768:Obidoxime Chloride