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

Ji-Young Park; Kyoung Ah Kim

doi:10.1007/s00228-003-0641-z

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

Ji-Young Park, Kyoung Ah Kim

Research output: Contribution to journal › Article

20 Citations (Scopus)

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.

Original language	English
Pages (from-to)	407-409
Number of pages	3
Journal	European Journal of Clinical Pharmacology
Volume	59
Issue number	5-6
DOIs	https://doi.org/10.1007/s00228-003-0641-z
Publication status	Published - 2003 Sep 1
Externally published	Yes

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Keywords

5-Fluorouracil (5-FU)
Cytochrome P
Warfarin

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

Cite this

Park, J-Y., & Kim, K. A. (2003). Inhibitory effect of 5-fluorouracil on human cytochrome P₄₅₀ isoforms in human liver microsomes. European Journal of Clinical Pharmacology, 59(5-6), 407-409. https://doi.org/10.1007/s00228-003-0641-z

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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.",

keywords = "5-Fluorouracil (5-FU), Cytochrome P, Warfarin",

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N2 - 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.

AB - 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.

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10.1007/s00228-003-0641-z