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- Title
Inhibitory effect of 5-fluorouracil on human cytochrome P<sub>450</sub> isoforms in human liver microsomes.
- Authors
Park, Ji-Young; Kim, Kyoung-Ah
- Abstract
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.
- Subjects
DRUG side effects; DRUG interactions; FLUOROURACIL; ANTINEOPLASTIC agents; METABOLISM; BIOCHEMISTRY
- Publication
European Journal of Clinical Pharmacology, 2003, Vol 59, Issue 5/6, p407
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-003-0641-z