Obidoxime in acute organophosphate poisoning: 2 - PK/PD relationships.
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.
Bundeswehr Institute of Pharmacology and Toxicology, Sanitätsakademie der Bundeswehr, Munich, Germany.
Horst
H
Thiermann
Franz
F
Worek
Peter
P
Eyer
Florian
F
Eyer
Norbert
N
Felgenhauer
Thomas
T
Zilker
D000110:Acetylcholinesterase / Q000097:blood; D000208:Acute Disease; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001285:Atropine / Q000493:pharmacokinetics / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002802:Cholinesterases / Q000097:blood; D003422:Critical Care; D004117:Dimethoate / Q000493:pharmacokinetics / Q000506:poisoning; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D062787:Drug Overdose / Q000188:drug therapy / Q000401:mortality; D004912:Erythrocytes / Q000201:enzymology; D005858:Germany / Q000453:epidemiology; D006801:Humans; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009768:Obidoxime Chloride / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009946:Organothiophosphorus Compounds / Q000506:poisoning*; D010278:Parathion / Q000506:poisoning; D013405:Suicide; D016896:Treatment Outcome
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009946:Organothiophosphorus Compounds; D009768:Obidoxime Chloride; D010278:Parathion; D001285:Atropine; C026086:methyl demeton; D000110:Acetylcholinesterase; D002802:Cholinesterases; D004117:Dimethoate