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

Ji-Young Park, Kyoung Ah Kim

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)407-409
Number of pages3
JournalEuropean Journal of Clinical Pharmacology
Volume59
Issue number5-6
DOIs
Publication statusPublished - 2003 Sep 1
Externally publishedYes

Fingerprint

Liver Microsomes
Fluorouracil
Cytochrome P-450 Enzyme System
Protein Isoforms
Drug Interactions
Pharmaceutical Preparations
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2E1
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP2D6
Liver

Keywords

  • 5-Fluorouracil (5-FU)
  • Cytochrome P
  • Warfarin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Inhibitory effect of 5-fluorouracil on human cytochrome P450 isoforms in human liver microsomes. / Park, Ji-Young; Kim, Kyoung Ah.

In: European Journal of Clinical Pharmacology, Vol. 59, No. 5-6, 01.09.2003, p. 407-409.

Research output: Contribution to journalArticle

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AU - Kim, Kyoung Ah

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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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