Obidoxime in acute organophosphate poisoning: 2 - PK/PD relationships

Clin Toxicol (Phila). 2009 Sep;47(8):807-13. doi: 10.1080/15563650903206836.

Abstract

Objective: The effects of obidoxime in the treatment of organophosphate poisoning were assessed by biochemical and biological effect monitoring. In this article we report effects on neuromuscular function, oxime and atropine concentration, and relate them to acetylcholinesterase (AChE) activity.

Methods: We measured the activity of cholinesterase in plasma and AChE in red blood cells (RBC) and related these data with neuromuscular transmission analysis (ulnar nerve stimulation). Concomitantly, poison and oxon along with plasma obidoxime and atropine levels were measured at regular intervals.

Results: We found a close correlation between RBC-AChE activity and neuromuscular transmission and a reciprocal correlation between both the atropine maintenance dose and/or its plasma concentration. The steady state of RBC-AChE activity of reactivation and re-inhibition followed the course predicted by laboratory-determined reaction constants.

Conclusions: Intense monitoring of organophosphate-poisoned patients allowed assessment of why a given obidoxime concentration was, or was not, able to counteract the re-inhibition of the RBC-AChE. RBC-AChE activity mirrors the function of n-receptor- and m-receptor-mediated cholinergic signaling as measured by neuromuscular transmission and atropine requirements.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / blood
  • Acute Disease
  • Antidotes / administration & dosage
  • Antidotes / pharmacokinetics*
  • Antidotes / therapeutic use*
  • Atropine / pharmacokinetics
  • Atropine / therapeutic use
  • Cholinesterase Inhibitors / poisoning*
  • Cholinesterase Reactivators / administration & dosage
  • Cholinesterase Reactivators / pharmacokinetics*
  • Cholinesterase Reactivators / therapeutic use*
  • Cholinesterases / blood
  • Critical Care
  • Dimethoate / pharmacokinetics
  • Dimethoate / poisoning
  • Drug Administration Schedule
  • Drug Monitoring
  • Drug Overdose / drug therapy
  • Drug Overdose / mortality
  • Erythrocytes / enzymology
  • Germany / epidemiology
  • Humans
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / metabolism
  • Obidoxime Chloride / administration & dosage
  • Obidoxime Chloride / blood
  • Obidoxime Chloride / pharmacokinetics*
  • Obidoxime Chloride / therapeutic use*
  • Organothiophosphorus Compounds / poisoning*
  • Parathion / poisoning
  • Suicide
  • Treatment Outcome

Substances

  • Antidotes
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Organothiophosphorus Compounds
  • Obidoxime Chloride
  • Parathion
  • Atropine
  • methyl demeton
  • Acetylcholinesterase
  • Cholinesterases
  • Dimethoate