Ji-Young Park1, Kyoung-Ah Kim. 1. Department of Pharmacology, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, 405-760 Incheon, Korea. jypark@gachon.ac.kr
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 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. 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.
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. 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.
Authors: K E Thummel; D D Shen; T D Podoll; K L Kunze; W F Trager; C E Bacchi; C L Marsh; J P McVicar; D M Barr; J D Perkins Journal: J Pharmacol Exp Ther Date: 1994-10 Impact factor: 4.030
Authors: D Sesardic; A R Boobis; B P Murray; S Murray; J Segura; R de la Torre; D S Davies Journal: Br J Clin Pharmacol Date: 1990-06 Impact factor: 4.335