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Inhibitory Effect of 5-Fluorouracil on Cytochrome P450 2C9 Activity in Cancer Patients
| Content Provider | Scilit |
|---|---|
| Author | Gunes, Arzu Coskun, Ugur Boruban, Cem Gunel, Nazan Babaoğlu, Melih O. Sencan, Orhan Bozkurt, Atila Rane, Anders Hassan, Moustapha Zengil, Hakan Yasar, Umit Bozkurt, Atilla |
| Copyright Year | 2006 |
| Description | Journal: Basic & Clinical Pharmacology & Toxicology 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. |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1742-7843.2006.pto_304.x/pdf |
| Ending Page | 200 |
| Page Count | 4 |
| Starting Page | 197 |
| e-ISSN | 17427843 |
| DOI | 10.1111/j.1742-7843.2006.pto_304.x |
| Journal | Basic & Clinical Pharmacology & Toxicology |
| Issue Number | 2 |
| Volume Number | 98 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2006-02-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Basic & Clinical Pharmacology & Toxicology Pharmacology and Pharmacy Colorectal Cancer Cytochrome P450 2c9 Fluorouracil and Cytochrome |
| Content Type | Text |
| Resource Type | Article |
