Title
Kinetic profile in blood and brain of the cholinesterase reactivating oxime HI-6 after intravenous administration to the rat
Author
Prins Maurits Laboratorium TNO
Ligtenstein, D.A.
Kossen, S.P.
Publication year
1983
Abstract
The kinetic profile of the oxime HI-6, a potent cholinesterase reactivator, after iv administration of 0.1325 mmol/kg (50 mg/kg) to rats is described. The blood concentrations measured over a period of 300 min can be described by a two-compartment open model. Excretion occurred only by the kidney. Approximately 60% was excreted in unmetabolized form. Brain tissue concentrations were significantly above the detection limit of the HPLC analysis procedure even when a correction was made for the amount of HI-6 present in brain blood. The concentration in brain tissue is built up according to a rapid equilibration mechanism. Disappearance of HI-6 from brain brain occurred slowly compared to the elimination of HI-6 from blood. These findings are discussed in the light of the existing knowledge on the kinetic behavior of polar solutes in the central nervous system. Whether the concentrations of HI-6 built up in the brain are relevant for the therapy of organophosphate intoxications cannot be determined from the experiments described. Chemicals/CAS: 1 (4 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether, 34433-31-3; HI 6, 34433-31-3; Pyridinium Compounds
Subject
1 (4 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether
animal experiment
blood and hemopoietic system
central nervous system
controlled study
drug bile level
drug blood level
drug brain level
drug distribution
drug elimination
drug feces level
drug metabolism
drug monitoring
drug tissue level
drug urine level
high performance liquid chromatography
intravenous drug administration
nonbiological model
nonhuman
pharmacokinetics
pyridinium aldoxime
Animal
Blood
Brain
Chromatography, High Pressure Liquid
Kinetics
Male
Pyridinium Compounds
Rats
Rats, Inbred Strains
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DOI
https://doi.org/10.1016/0041-008x(83)90334-4
TNO identifier
229489
ISSN
0041-008X
Source
Toxicology and Applied Pharmacology, 71 (71), 177-183
Document type
article