Comparative studies on the metabolism of new fluorinated pyrimidine drugs in the liver by in vivo 19F 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 suppression of 5-FU catabolism by CNDP were observed by in vivo 19F 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-beta-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.
Harada
M
M
Department of Radiology, School of Medicine, University of Tokushima.
Nishitani
H
H
Koga
K
K
Miura
I
I
Kimura
A
A
D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D050744:Dihydrouracil Dehydrogenase (NAD+); D004347:Drug Interactions; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005641:Tegafur / Q000378:metabolism; D014498:Uracil / Q000378:metabolism*
D011725:Pyridines; D005641:Tegafur; C053195:2,6-dihydroxy-3-cyanopyridine; C007742:3-fluoroalanine; D014498:Uracil; C059823:1-ethoxymethyl-5-fluorouracil; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050744:Dihydrouracil Dehydrogenase (NAD+); D000409:Alanine; D005472:Fluorouracil