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Comparative Studies on the Metabolism of New Fluorinated Pyrimidine Drugs in the Liver by in vivo(19)F Magnetic Resonance Spectroscopic Observation

1‐Ethoxymethyl‐5‐fluorouracil (EM‐FU) is a fluorinated pyrimidine derived from 5‐FU, and 3‐cyano‐2,6‐dihydroxypyridine (CNDP) is a chemical modulator which suppresses the catabolism of 5‐FU by inhibiting dihydrouracil dehydrogenase in the liver. In this study, the metabolism of EM‐FU and the suppres...

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Detalles Bibliográficos
Autores principales: Harada, Masafumi, Nishitani, Hiromu, Koga, Keiko, Miura, Iwao, Kimura, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1993
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919136/
https://www.ncbi.nlm.nih.gov/pubmed/8463136
http://dx.doi.org/10.1111/j.1349-7006.1993.tb02855.x
Descripción
Sumario:1‐Ethoxymethyl‐5‐fluorouracil (EM‐FU) is a fluorinated pyrimidine derived from 5‐FU, and 3‐cyano‐2,6‐dihydroxypyridine (CNDP) is a chemical modulator which suppresses the catabolism of 5‐FU by inhibiting dihydrouracil dehydrogenase in the liver. In this study, the metabolism of EM‐FU and the suppression of 5‐FU catabolism by CNDP were observed by in vivo(19)F magnetic resonance spectroscopy in comparison with other similar drugs, because it is considered that the most effective mode of therapy using 5‐FU is to suppress the catabolism of 5‐FU in the liver and so to maintain for longer an effective blood level of 5‐FU. The metabolism of EM‐FU was very slow and the production of fluoro‐β‐alanine was very low as compared to the case of tegafur. The catabolic suppression by CNDP was much stronger than that of uracil. Therefore co‐administration of EM‐FU and CNDP should suppress catabolism and maintain an effective blood level of 5‐FU for a long period of time.