Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF)

Eyer, Florian, Roberts, Darren M., Buckley, Nicholas A., Eddleston, Michael, Thiermann, Horst, Worek, Franz and Eyer, Peter (2009) Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF). Biochemical Pharmacology, 78 5: 531-537. doi:10.1016/j.bcp.2009.05.004

Author Eyer, Florian
Roberts, Darren M.
Buckley, Nicholas A.
Eddleston, Michael
Thiermann, Horst
Worek, Franz
Eyer, Peter
Title Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF)
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 2009-09-01
Sub-type Article (original research)
DOI 10.1016/j.bcp.2009.05.004
Volume 78
Issue 5
Start page 531
End page 537
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract Chlorpyrifos (CPF) is a pesticide that causes tens of thousands of deaths per year worldwide. Chlorpyrifos oxon (CPO) is the active metabolite of CPF that inhibits acetylcholinesterase. However, this presumed metabolite has escaped detection in human samples by conventional methods (HPLC, GC-MS, LC-MS) until now. A recently developed enzyme-based assay allowed the determination of CPO in the nanomolar range and was successfully employed to detect this metabolite. CPO and CPF were analysed in consecutive plasma samples of 74 patients with intentional CPF poisoning. A wide concentration range of CPO and CPF was observed and the ratio of CPO/CPF varied considerably between individuals and over time. The ratio increased during the course of poisoning from a mean of 0.005 in the first few hours after ingestion up to an apparent steady-state mean of 0.03 between 30 and 72 h. There was a hundred-fold variation in the ratio between samples and the interquartile range (between individuals) indicated over half the samples had a 5-fold or greater variation from the mean. The ratio was independent of the CPF concentration and the pralidoxime regimen. CPO was present in sufficient quantities to explain any observed acetylcholinesterase inhibitory activity. The effectiveness of pralidoxime in reactivating the inhibited acetylcholinesterase is strongly dependent on the CPO concentration. Differences in clinical outcomes and the response to antidotes in patients with acute poisoning may occur due to inter-individual variability in metabolism.
Keyword Organophosphorus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Thu, 03 Sep 2009, 07:46:20 EST by Mr Andrew Martlew on behalf of School of Medicine