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

Abstract

In vivo fluorine 19 nuclear magnetic resonance ¹⁹F 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 chemotherapeutic agents (methotrexate, leucovorin, or levarnisole) either prophylac­ tically after breast cancer surgery or for colorectal cancer. The time constant for the disappearance of 5-FU from the liver in vivo varied from S to 17 min, while the time constant for the appearance of α-fluoro-β-alanine (the major catabolite of 5-FU) varied from 7 to 86 min. The modulators of 5-FU metabolism did not appear to affect the time constant for the disappearance of 5-FU from the liver or for the appearance of α-fluoro-β-alanine. Results obtained indicate that the pharmacokineties of S-FU and α-fluoro-β-alanine may vary substantially at different times in a given individual.