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 › peer-review

21 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

Keywords

5-Fluorouracil (5-FU)
Cytochrome P
Warfarin

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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title = "Inhibitory effect of 5-fluorouracil on human cytochrome P450 isoforms in human liver microsomes",

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",

author = "Park, {Ji Young} and Kim, {Kyoung Ah}",

year = "2003",

month = sep,

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doi = "10.1007/s00228-003-0641-z",

language = "English",

volume = "59",

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journal = "European Journal of Clinical Pharmacology",

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TY - JOUR

T1 - Inhibitory effect of 5-fluorouracil on human cytochrome P450 isoforms in human liver microsomes

AU - Park, Ji Young

AU - Kim, Kyoung Ah

PY - 2003/9/1

Y1 - 2003/9/1

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.

KW - 5-Fluorouracil (5-FU)

KW - Cytochrome P

KW - Warfarin

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