RESEARCH ARTICLE


Dose-Dependent Tissue Distribution of K117, a Bis-pyridinium Aldoxime, in Rats



Huba Kalász1, *, Gellért Karvaly2, Kamil Musilek3, Kamil Kuca3, Jung Young-Sik4, Barbara Malawska5, Ernest A. Adeghate6, Syed M. Nurulain7, Judit Szepesy1, Tibor Zelles1, Kornélia Tekes8
1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Orczy út 2-4, Hungary
2 Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Orczy út 2-4, Hungary
3 Department of Chemistry, University of Hradec Kralove, 500 03 Hradec Kralove, Rokitanskeho 62, Czech Republic
4 Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
5 Department of Physicochemical Drug Analysis, Jagiellonian University, 30688 Krakow, ul. Mediczna 9, Poland
6 Department of Anatomy, College of Medicine, United Arab Emirates University, 17666, Al Ain, UAE
7 Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
8 Department of Pharmacodynamics, Semmelweis University, 1089 Budapest, Orczy út 2-4, Hungary


© 2019 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, 1089 Budapest, Orczy út 2-4, Hungary; Tel: +36302747986; Fax: +3612104412; E-mail: drkalasz@gmail.com


Abstract

Background:

Bis-pyridinium aldoximes are reactivators of the paraoxon-inhibited butyrylcholinesterase enzyme. Paraoxon is the active product of parathion, a widely used insecticide.

Objective:

The objective of this study is to examine the dose-dependent distribution of K117, a bis-pyridinium aldoxime in rat tissues.

Materials and Methods:

White male Wistar rats were intramuscularly injected with various doses of K117; the animals were sacrificed 30 minutes after injections. The dose-dependent body distribution of K117 was determined using reversed-phase HPLC.

Results:

Dose-dependent distribution of K117 in body tissues was linear in the serum and other body tissues throughout the whole range of the concentrations studied. However, the of distribution was not observed in the brain and cerebrospinal fluid, especially with high doses.

Conclusion:

The body distribution of K117 significantly depends on doses used, the p-value is: 500 nmol, i.m., when applied in the range of 100 to 10,000 nmol.

Keywords: K117, Dose-dependence, Pharmacokinetics, Wistar rats, Intramuscular injections, Linear Pattern.