Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 33, Issue 1, Pages 18-23Publisher
WILEY
DOI: 10.1002/jat.1699
Keywords
cholinesterase reactivator; oxime; pharmacokinetics; HPLC; plasma; trimedoxime; K027
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Funding
- Ministry of Defence (Czech Republic) [OPUOFVZ200604]
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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 1100 mu g 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 mu g ml-1, P?=?0.72) and AUC0180min (2290 +/- 304 vs 2269 +/- 197?min mu g 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?
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