Antidotal Efficacy and Pharmacokinetics of HI-6 and Trimedoxime in Mice Poisoned with Soman or Paraoxon
Abstract
The aim of this work was to examine and correlate the pharmacokinetic, reactivating and protective properties of HI-6 and trimedoxime in mice poisoned with soman or paraoxon. Male albino mice were poisoned with 1.3 LD-50 iv of soman or paraoxon, at different time intervals after iv administration of the antidotes. Median effective doses and efficacy half times were calculated. In the biochemical set of experiments, brain, diaphragmal and erythrocyte acetyicholinesterase activities were determined. To obtain values of pharmacokinetic parameters, oximes were administered intravenously and analysed in plasma samples by MPLC method. Oxime concentrations versus time curves were estimated using a two-compartment open model. When HI-6 was applied in soman poisoned animals, acetyleholinesterase activity recovered to 69.30 % and 34.67 % of the control diaphragmal and erythrocyte acetyleholinesterase activity, respectively. In paraoxon treated animals, use of trimedoxime produced significant increase of acetylcholinesterase activity in all examined tissues. Plasma concentrations of oximes reached maximum values immediately after injection, and then decreased rapidly due to the transport of oximes to the peripheral compartment and elimination. From the calculated phaimacokinetic parameters, it appears that trimedoxime penetrates the tissues better, is slowly transferred back to the circulation and remains longer in the body. In spite of pharmacokinetic data obtained for trimedoxime, it was practically ineffective against soman poisoning, indicating that antidotal efficacy depends much more on the reactivation potency of the oximes than on their pharmacokinetics. However, better insight into the pharmacokinetic profile of oximes is necessary in order to optimize the antidotal therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADP013410
Entities
People
- Biljana Antonijevic
- Matej Maksimovic
- Milos P. Stojiljkovic
- Vesna Kilibarda
- Zoran A. Milovanovic
Organizations
- Military Medical Academy