Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and newly synthesized oxime K027, in rat plasma

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?