Abstract
2052 Background: The extensive use of 5-fluorouracil (5-FU) has attracted a great attention on dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for detoxification of 5-FU to 5-fluoro-5,6-dihydrouracil (5-FDHU). The incidence of DPD deficiency is estimated to be around 3% and thus the related 5-FU life-threatening toxicity has significant clinical implications. Methods: In order to (1) investigate the clinical pharmacokinetics (PK) of 5-FU/5-FDHU in cancer patients administered with a 5-FU single low dose, (2) predict the systemic impairment of 5-FU catabolism and (3) prevent severe drug-related toxicity, 112 patients received 5-FU 250 mg/m2 as i.v. bolus before starting the planned 5-FU treatment (i.v. bolus of 370 mg/m2/day 5-FU for 5 days, or continuos infusion of 3800 mg/m2 5-FU for 48 h). HPLC analysis was performed on plasma (from 0 to 1.5 h after 5-FU) and peripheral blood mononuclear cell samples to calculate 5-FU/5-FDHU PK parameters and DPD activity, respectively. Adverse events were...
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