Pharmacokinetics of orally administered uracil in healthy volunteers and in DPD-deficient patients, a possible tool for screening of DPD deficiency

摘要: Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to severe toxicity in patients treated with standard doses of 5-fluorouracil (5-FU). Oral uracil administration and subsequent measurement dihydrouracil (DHU) plasma concentrations might detect DPD deficiency. This study compares the pharmacokinetics DHU after oral subjects normal deficient status. Five hundred milligrams per metre square was administered orally 11 status 10 reduced activity. Repeated (n = 3) this dose performed 4 subjects, 1,000 mg uracil/m2 assess intra-individual variation linearity pharmacokinetics. In status, 500 mg/m2 resulted C max levels 14.4 ± 4.7 mg/L at T max = 30.0 ± 11.6 min, DPD-deficient 20.0 ± 4.5 mg/L 31.5 ± 1.1 min. The AUC0>180 31.2 ± 5.1 mg L/h which significantly higher (P < 0.05) than (13.8 ± 3.9 mg L/h). dosing showed reproducible PK elevation suggested linear differs between a activity those AUC be useful as diagnostic tool differentiate regard