Pharmacokinetics of a mono-pyridinium-mono-aldoxime (K-347), a potential antidote in organophosphate poisoning

Abstract

Background: Our recent work has been treating the pharmacokinetics of pyridinium aldoximes of various structures including their time-dependent distribution in the body of male rats and also the extent of blood-brain-barrier penetration. Objective: Our overall aim was to find a proper antidote in organophosphate poisoning with fast elimination. Methods: White male Wistar rats were intramuscularly injected with the aqueous solution of 3 µmol of K-347. The animals were sacrificed at different time periods following treatment; various tissues and body fluids were taken and homogenised. The level of K-347 was determined using reversed-phase HPLC. Dose-dependence of tissue level was also determined by using various doses, 3 µmol through 100 µmol of K-347. Results: The serum level of K-347 showed a definitely fast decline. K347 did not have any effect on Gram-positive and Gram-negative bacteria that we tested. Conclusion: The kinetics of K-347 showed an extremely fast offset, even in comparison with several other pyridinium aldoximes in clinical practice and in developmental stages. © 2020 Kalász et al.