Effect of L-cysteine on plasma concentration and urinary excretion of 1-(tetrahydro-2-furanyl)-5-fluorouracil metabolites.
Effects of L-cysteine (CySH) on the plasma concentrations and the urinary excretion of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its metabolites were studied by high performance liquid chromatography in rats. Significantly higher plasma concentrations of FT, 5-fluorouracil (5-FU) and cis-4'-OH-FT were obtained after an oral administration of FT (500 mg/kg) combined orally with CySH (500 mg/kg) when compared to FT alone. The urinary excretions of 5-FU, trans-3'-OH-FT, cis-4'-OH-FT, trans-4'-OH-FT and 4',5'-dehydro-FT significantly decreased up to 12 h but that of alpha-fluoro-beta-alanine significantly increased up to 24 h by the combined administration of CySH. Furthermore, the plasma concentration of 5-FU significantly increased at 0.5 h and its urinary excretion significantly decreased up to 4 h after an intraperitoneal administration of 5-FU (10 mg/kg) combined orally with CySH (500 mg/kg) when compared to 5-FU alone. The urinary pH significantly changed to acidic and the urinary volume significantly increased by the combined administration of CySH, so it was thought that the reabsorption of 5-FU through renal tubules from urine could increase and the increment of the urinary excretion of alpha-fluoro-beta-alanine was caused by this. Then it was suggested that the increase of the plasma concentrations of 5-FU and cis-4'-OH-FT could be attributed to the decrease of their urinary excretions after an administration of FT combined with CySH when compared to FT alone.
Kawabata
N
N
Central Research Laboratory, SS Pharmaceutical Co., Ltd., Narita, Japan.
Yano
K
K
Ohno
H
H
Nakashima
T
T
D000818:Animals; D003545:Cysteine / Q000494:pharmacology*; D005472:Fluorouracil / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D005641:Tegafur / Q000378:metabolism*
D005641:Tegafur; D003545:Cysteine; D005472:Fluorouracil