| Literature DB >> 16445595 |
Arzu Gunes1, Ugur Coskun, Cem Boruban, Nazan Gunel, Melih O Babaoglu, Orhan Sencan, Atila Bozkurt, Anders Rane, Moustapha Hassan, Hakan Zengil, Umit Yasar.
Abstract
Drug interactions have been reported between 5-fluorouracil and cytochrome P450 2C9 (CYP2C9) substrates, S-warfarin and phenytoin. This study was performed to determine the influence of 5-fluorouracil on cytochrome P450 2C9 (CYP2C9) activity in colorectal cancer patients (n=17) receiving 5-fluorouracil. Losartan was used as a marker to assess CYP2C9 activity. Losartan and its CYP2C9 dependent metabolite, E-3174, were determined in urine. The ratios of urinary losartan/E-3174 before and after the 5-fluorouracil treatment were compared for each patient. Genotyping was performed to detect the CYP2C9*2 and CYP2C9*3. At the end of the first cycle of 5-fluorouracil, losartan/E-3174 ratio was increased by 28.0% compared to the pre-treatment values (P=0.15). In five patients recruited for phenotyping after three 5-fluorouracil cycles, the metabolic ratio was increased significantly by 5.3 times (P=0.03). The results suggest that in most patients 5-fluorouracil inhibited CYP2C9 activity. This inhibition was more pronounced when the total administered dose increased. This finding may help explain the mechanism of interaction between 5-fluorouracil and CYP2C9 substrates.Entities:
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Year: 2006 PMID： 16445595 DOI： 10.1111/j.1742-7843.2006.pto_304.x
Source DB: PubMed Journal: Basic Clin Pharmacol Toxicol ISSN： 1742-7835 Impact factor: 4.080