Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds

H Thiermann1, F Eyer, N Felgenhauer

  • 1Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany. HorstThiermann@bundeswehr.org

Toxicology Letters
|June 15, 2010
PubMed
Abstract

Insights

This study shows that a specific obidoxime regimen effectively achieves therapeutic plasma levels for organophosphorus poisoning treatment. The treatment was well-tolerated and suitable for mass casualty events.

Area of Science:

  • Pharmacology
  • Toxicology
  • Emergency Medicine

Background:

  • Organophosphorus (OP) compounds inhibit acetylcholinesterase (AChE), leading to poisoning.
  • Oximes are crucial for reactivating inhibited AChE, serving as a causal therapy for OP intoxication.
  • Optimal oxime therapy requires prompt administration of effective doses to maximize reactivation potential.

Purpose of the Study:

  • To assess the achievement of a target obidoxime plasma concentration (10-20 microM) in severely OP-poisoned patients.
  • To evaluate the efficacy and tolerability of a specific obidoxime regimen in achieving therapeutic levels.

Main Methods:

  • A cohort of 34 severely OP-poisoned patients received an obidoxime regimen (250 mg IV bolus, then 750 mg/24h) in the ICU.
  • Plasma obidoxime concentrations were monitored using High-Performance Liquid Chromatography (HPLC).
  • The regimen was maintained as long as AChE reactivation was possible.

Main Results:

  • The regimen resulted in a mean steady-state plasma obidoxime concentration of 14.5+/-7.3 microM, within the target range.
  • A total of 2269+/-1726 mg of obidoxime was infused over 65+/-55 hours.
  • Obidoxime exhibited biphasic elimination (t1/2(1)=2.2h, t1/2(2)=14h) and accumulated in tissues like cartilage, kidney, and liver.

Conclusions:

  • The proposed obidoxime regimen successfully achieved the targeted therapeutic plasma concentrations in OP-poisoned patients.
  • Obidoxime demonstrated biphasic elimination and was well-tolerated, indicating a favorable safety profile.
  • This regimen is recommended for adults, even in mass casualty scenarios involving OP poisoning.

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