Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and newly synthesized oxime K027, in rat plasma
Article first published online: 30 JUN 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 1, pages 18–23, January 2013
How to Cite
Karasova, J. Z., Chladek, J., Hroch, M., Josef, F., Hnidkova, D. and Kuca, K. (2013), Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and newly synthesized oxime K027, in rat plasma. J. Appl. Toxicol., 33: 18–23. doi: 10.1002/jat.1699
- Issue published online: 29 NOV 2012
- Article first published online: 30 JUN 2011
- Manuscript Revised: 18 APR 2011
- Manuscript Accepted: 18 APR 2011
- Manuscript Received: 3 MAR 2011
- cholinesterase reactivator;
K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)–propane dibromide] is a promising new reactivator of organophosphate- or organophosphonate-inhibited acetylcholinesterase (AChE) with low acute toxicity and broad spectrum efficacy. The aim of the present study was to compare the pharmacokinetics of both compounds. Male Wistar rats (body weight = 320 ± 10 g) were administered a single intramuscular dose of K027 (22.07 mg kg−1) and an equimolar dose of trimedoxime. Blood was collected at various time intervals until 180 min. Plasma samples were analyzed by reversed-phase HPLC with ultraviolet (UV) detection. The recovery of both oximes from the plasma was approximately 90% and a linear relationship (R2 > 0.998) was observed between the peak areas and concentrations of calibrated standards in the range 1–100 µg ml−1. Near-identical plasma profiles were obtained for both compounds. No differences were found in the mean ± SD values of Cmax (18.6 ± 2.5 vs 20.0 ± 6.3 µg ml−1, P = 0.72) and AUC0–180min (2290 ± 304 vs 2269 ± 197 min µg ml−1, P = 0.84). However, the percentage coefficient of variation of the first-order rate constant of absorption (ka) was 3-fold higher (P < 0.01) providing evidence for more erratic absorption of intramuscular trimedoxime as compared with K027. In conclusion, oxime K027 might have superior pK properties that may be translated in its faster absorption and subsequent tissue distribution. Copyright © 2011 John Wiley & Sons, Ltd.