Inhibitory effect of 5-fluorouracil on human cytochrome P(450) isoforms in human liver microsomes.
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.


CONCLUSIONS
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.
Park
Ji-Young
JY
Department of Pharmacology, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, 405-760 Incheon, Korea. jypark@gachon.ac.kr
Kim
Kyoung-Ah
KA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D005472:Fluorouracil