Abstract

The comparative saliva/plasma pharmacokinetics of 5-fluorouracil (5-FU) were investigated in 21 patients with metastatic colorectal cancer receiving high-dose folinic acid (LV (leucovorin) 200 mg/m2) followed by 5-FU bolus (400 mg/m2) and continuous infusion (600, 750, 900 or 1200 mg/m2) on days 1 and 2. Quantitation of unchanged drug was assessed by a highly specific high-performance liquid chromatographic method. Large patient-to-patient variations in plasma and saliva 5-FU concentrations were observed. Saliva pharmacokinetics could be described using a bi-exponential pattern. The half-life of the rapid phase averaged 8.0 min, and was of the same order of magnitude as the 5-FU elimination half-life determined from plasma data. The half-life of the terminal part of the curve averaged 8 h; such decrease in salivary concentrations could be due to changes in salivary gland function caused by 5-FU, which results in reduced salivary flow rate. Between individual 5-FU concentrations in parotid saliva and plasma a statistically significant straight line could be fitted with a coefficient of correlation of 0.675. Moreover, the risk of developing 5-FU-related mucositis was significantly linked to 5-FU salivary exposure. Diarrhoea was the most frequent toxicity encountered during the trial.