In vitro and in vivo metabolisms of K-48 |
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| Authors: | B Benkő H Kalász K Ludányi G Petroianu K Kuca F Darvas K Tekes |
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| Institution: | 1.Division of Pharmacology and Drug Safety,Richter Gedeon Rt., Gy?mr?i út 21,Budapest,Hungary;2.Department of Pharmacology and Pharmacotherapy,Semmelweis University,Budapest,Hungary;3.Department of Pharmacology & Therapeutics, Faculty of Medicine & Health Sciences,United Arab Emirates University,Al Ain,United Arab Emirates;4.Department of Pharmaceutics,Semmelweis University,Budapest,Hungary;5.Department of Toxicology,Faculty of Military Health Sciences,Hradec Kralove,Czech Republic;6.ComInnex Zrt,Budapest,Hungary;7.Department of Pharmacodynamics,Semmelweis University,Budapest,Hungary |
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| Abstract: | 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 μmol 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.
Figure Suggested metabolic pathways of K-48 |
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| Keywords: | Microsomal metabolism Cholinesterase reactivator K-48 In vivo metabolism HPLC– MS |
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