In vitro and in vivo metabolisms of K-48.
Metabolic pathways of the oxime K-48 have been elucidated by means of in vitro and in vivo experiments. K-48 exposure to rat liver microsomal fraction resulted in the formation of a hydroxylated derivative, in addition to a small molecular fragment. The in vivo metabolism in rats was investigated after intramuscular administration of 50 mumol oxime. K-48 was present in the rat serum in unchanged form. Similarly, the analysis of rat cerebrospinal fluid indicated the sole occurrence of unchanged K-48. In contrast, unchanged K-48 was not found in the rat urine, where only the metabolite generated by epoxidation on the alkyl chain connecting the two pyridinium rings was present. The presence of unchanged K-48 in the serum and cerebrospinal fluid facilitates quantitative determination using HPLC separation and ultraviolet absorbance detection.
Benko
B
B
Division of Pharmacology and Drug Safety, Richter Gedeon Rt, Gyömroi út 21, 1475, Budapest, Hungary.
Kalász
H
H
Ludányi
K
K
Petroianu
G
G
Kuca
K
K
Darvas
F
F
Tekes
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism; D002801:Cholinesterase Reactivators / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D003640:Dealkylation; D004852:Epoxy Compounds / Q000378:metabolism; D006900:Hydroxylation; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D010091:Oximes / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
D002801:Cholinesterase Reactivators; D004852:Epoxy Compounds; C520230:K-48 compound; D010091:Oximes