Influence of metastatic disease on the usefulness of uracil pharmacokinetics as a screening tool for DPD activity in colorectal cancer patients.

摘要: Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to severe toxicity in patients treated with a standard dose of fluoropyrimidine such as 5-fluorouracil or capecitabine (CAP). Administration oral uracil and subsequent measurement dihydrouracil (DHU) plasma concentrations has been used identify DPD deficiency. Liver metastasis might influence systemic activity. The aim the study was investigate effect metastatic disease on pharmacokinetics DHU after administration uracil. 500 mg/m2 administered orally 12 subjects stages II–III colorectal cancer (CRC) who were adjuvant setting stage IV metastasized CRC, all CAP containing therapy. All had normal activity defined >6 nmol/mg/h determined peripheral blood mononuclear cells. mean clearance [CL 51.7 (SD 6.4) vs. 46.7 13.0) l/h], area under curve [AUC0–220min 20.6 21.0 5.7) h mg/l], elimination half-life [t 1/2 21 7) 8) min], maximum concentration time [T max 27 9) 25 volume distribution [V 26.58 10.11) 21.10 8.48) l] constant [k el 2.01 0.56) 2.41 0.72) h−1] did not differ significantly (p > 0.05) non-metastatic CRD versus CRC. Metastasis does alter and is similar CRC without metastasis. Therefore, test could be phenotype both adjuvantly using cutoff criteria