RESEARCH ARTICLE


Pharmacokinetics of a Mono-pyridinium-mono-aldoxime (K-347), a Potential Antidote in Organophosphate Poisoning



Huba Kalász1, *, Gellért Karvaly2, Ferenc Szimrók1, Dóra Szabó3, Márton Milánkovits3, András Keglevich1, Jennifer Adeghate4, Ferenc Darvas5, Kamil Kuca6, Kamil Musilek6, Kornélia Tekes7
1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary
2 Department of Laboratory Medicine, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary
3 Department of Medical Microbiology, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary
4 Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, USA
5 ComInnex Inc., 1031 Budapest, Záhony utca 7, Hungary
6 Department of Chemistry, Faculty of Science, University of Hradec Kralove, 500 03 Hradec Kralove, Rokitanskeho 62, Czech Republic
7 Department of Pharmacodynamics, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary


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Creative Commons License
© 2020 Kalász et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary; E-mail drkalasz@gmail.com.


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.

Keywords: Pharmacokinetics, K-347, Time-dependence, Dose-dependence, Mono-pyridinium, Fast elimination, Absence of antibacterial effects.