Plasma and salivary pharmacokinetics of 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer receiving 5-FU bolus plus continuous infusion with high-dose folinic acid

The comparative saliva/plasma pharmacokinetics of 5-fluorouracil (5-FU) wer e investigated in 21 patients with metastatic colorectal cancer receiving h igh-dose folinic acid (LV (leucovorin) 200 mg/m(2)) followed by 5-FU bolus (400 mg/m(2)) and continuous infusion (600, 750, 900 or 1200 mg/m(2)) on da ys 1 and 2. Quantitation of unchanged drug was assessed by a highly specifi c high-performance Liquid chromatographic method. Large patient-to-patient variations in plasma and saliva 5-FU concentrations were observed. Saliva p harmacokinetics 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 mag nitude as the 5-FU elimination half-life determined from plasma data. The h alf-life of the terminal part of the curve averaged 8 h; such decrease in s alivary concentrations could be due to changes in salivary gland function c aused by 5-FU, which results in reduced salivary flow rate. Between individ ual 5-FU concentrations in parotid saliva and plasma a statistically signif icant straight line could be fitted with a coefficient of correlation of 0. 675. Moreover, the risk of developing 5-FU-related mucositis was significan tly linked to 5-FU salivary exposure. Diarrhoea was the most frequent toxic ity encountered during the trial. (C) 1999 Elsevier Science Ltd. All rights reserved.