title: Time-dependent changes of oxime K027 concentrations in different parts of rat central nervous system.
abstract: The blood-brain barrier plays a vital role in the protection of the central nervous system. It is composed of endothelial cells with tight-junctions to limit the penetration of many endogenous and exogenous compounds, particularly hydrophilic xenobiotics. Nerve agents and pesticides are groups of compounds with high penetration potential into the central nervous system. However, oxime type antidotes are known to penetrate blood-brain barrier only in low concentration. The aim of presented study is to describe the pharmacokinetic profile of oxime K027 a novel antidote candidate. The main focus is on penetration of tested substance into the selected brain regions following time-dependent manner. The maximum concentration of the oxime K027 was attaining 15 and 30 min after i.m. application in plasma and brain tissue, respectively. The perfused brain tissue concentration was relatively high (10(-7) M order of magnitude) and depending on the brain region it was constant 15-60 min after application. The highest concentration was found in the frontal cortex 15 min after application while the lowest measured concentration was determined in the basal ganglia. This study showed that oxime K027 is able to achieve high concentration level in perfused brain tissue relatively quickly, but also demonstrated rapid clearance from the central nervous system. These results are probably due to low overall uptake of oxime K027 into the brain.
authors.affiliation: Department of Public Health, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. karasova@pmfhk.cz
authors.forename: Jana Zdarova
authors.initials: JZ
authors.lastname: Karasova
authors.forename: Filip
authors.initials: F
authors.lastname: Zemek
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010091:Oximes / Q000378:metabolism* / Q000493:pharmacokinetics; D011726:Pyridinium Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: C481758:1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide; D010091:Oximes; D011726:Pyridinium Compounds