Abstract
This study investigated the relationship among the pharmacokinetics of 5-fluorouracil (5-FU) and 5-fluoro-5,6-dihydrouracil (5-FDHU); the activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells; and treatment-related toxicity in 26 patients with surgically resected colorectal cancer treated with short daily infusions of 5-FU adjuvant chemotherapy, each cycle consisting of 5 consecutive days every 4 weeks. After the first chemotherapeutic cycle, severe stomatitis and diarrhea occurred in 5 patients and were related to the variations in the systemic disposition of the drug rather than to DPD activity. These patients showed a significant decrease in 5-FU clearance, and an increase in the 5-FU/5-FDHU area under the time-concentration curve (AUC) ratio, as compared with patients who experienced mild toxicities, whereas a low DPD activity was observed in only 2 patients. In conclusion, the results of this study demonstrate that the alterations in 5-FU and 5-FDHU pharmacokinetics are related to severe toxicities in patients treated with short intravenous infusion of 5-FU.
Original language | English |
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Pages (from-to) | 588-593 |
Number of pages | 6 |
Journal | Therapeutic Drug Monitoring |
Volume | 24 |
Issue number | 5 |
DOIs | |
Publication status | Published - Oct 2002 |
Keywords
- 5-Fluorouracil
- Adjuvant chemotherapy
- Colorectal cancer
- Dihydropyrimidine dehydrogenase
- Toxicity
ASJC Scopus subject areas
- Toxicology
- Health, Toxicology and Mutagenesis
- Pharmacology
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology (medical)
- Public Health, Environmental and Occupational Health