Open AccessComparative Studies on the Metabolism of New Fluorinated Pyrimidine Drugs in the Liver by in vivo 19 F Magnetic Resonance Spectroscopic Observation
Author(s) -
Harada Masafumi,
Nishitani Hiromu,
Koga Keiko,
Miura Iwao,
Kimura Akio
Publication year - 1993
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1993.tb02855.x
Subject(s) - catabolism , in vivo , metabolism , tegafur , pyrimidine , uracil , chemistry , biochemistry , pyrimidine metabolism , phosphomonoesters , pharmacology , medicine , biology , enzyme , chemotherapy , purine , dna , microbiology and biotechnology , inorganic phosphate
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.