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Inhibitory effect of 5-fluorouracil on human cytochrome P(450) isoforms in human liver microsomes
1Department of Pharmacology, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, 405-760 Incheon, Korea. jypark@gachon.ac.kr
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 P(450) (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.
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