Metabolism of 5-fluorouracil in human liver: An in vivo F-19 NMR study

In vivo fluorine-19 nuclear magnetic resonance (F-19 NMR) spectroscopy was used to study the metabolism and pharmacokinetics of 5-fluorouracil (5-FU) in human liver. Nine patients received 5-FU, and additional chemotherapeuti c agents (methotrexate, leucovorin, or levamisole) either prophylactically after breast cancer surgery or for colorectal cancer. The time constant for the disappearance of 5-FU from the liver in vivo varied from 5 to 17 min, while the time constant for the appearance of a fluoro-beta-alanine (the ma jor catabolite of 5-FU) varied from 7 to 86 min. The modulators of 5-FU met abolism did not appear to affect the time constant for the disappearance of 5-FU from the liver or for the appearance of alpha-fluoro-beta-alanine. Re sults obtained indicate that the pharmacokinetics of 5-FU and alpha-fluoro- beta-alanine may vary substantially at different times in a given individua l.