Inhibitory effect of 5-fluorouracil on human cytochrome P₄₅₀ isoforms in human liver microsomes

Objective: A number of case reports have been described regarding drug interactions with 5-fluorouracil (5-FU) and co-administered drugs. However, little is known regarding the inhibitory potential of 5-FU on the metabolism of co-administered drugs by cytochrome P₄₅₀ (CYP). The aim of the present study was to elucidate the inhibitory effect of 5-FU on CYP isoforms using human liver microsomes. Methods: The inhibitory effect of 5-FU on CYP1A2, CYP2C9, CYP2C19, CYP2C8, CYP2E1, CYP2D6, and CYP3A4 activities was examined with specific probe drugs in human liver microsomes. Results: 5-FU showed little or no inhibitory effect on CYP-catalyzed reactions in human liver microsomal preparations. Conclusion: 5-FU has no inhibitory effect on CYP isoforms or drug metabolism causing drug interaction with 5-FU. The mechanism that causes drug interaction between co-administered drugs and 5-FU may not be related to direct CYP inhibition by 5-FU.