BACKGROUND:UFT is composed of tegafur, a prodrug of 5-fluorouracil, and uracil, at a fixed ratio of 1: 4. UFT is widely used with leucovorin as adjuvant chemotherapy in patients with colon cancer. As reported, UFT/leucovorin should not be taken simultaneously with food because a high fat content will reduce the systemic exposure to the active cytotoxic moiety of UFT. In this single-dose, randomized, two-way crossover study, we investigated the effects of a low-fat Japanese meal on the pharmacokinetics and oral bioavailability of UFT (2 x 100-mg capsules; dose in terms of tegafur) and leucovorin (1 x 25-mg tablet). METHODS:Patients (n = 12) were randomly assigned to receive both drugs after an overnight fast or 5 min after eating a standard Japanese breakfast (641 kcal), with a 3-day washout period between treatments. Pharmacokinetics (n = 12) were determined for tegafur, 5-fluorouracil, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin). RESULTS: For 5-fluorouracil pharmacokinetics, the maximum plasma concentration and the area under the curve were reduced by 73.7% and 47.4%, respectively, when UFT was taken postprandially, and the maximum plasma concentration and the area under the curve for uracil were reduced by 84.1% and 68.9%, respectively, compared with dosing on an empty stomach. These decreases in the systemic exposure to 5-fluorouracil were quite marked and may have an impact on its antitumor effect. CONCLUSION: A low-fat meal affects the pharmacokinetics of UFT similarly to a high-fat meal.
RCT Entities:
BACKGROUND:UFT is composed of tegafur, a prodrug of 5-fluorouracil, and uracil, at a fixed ratio of 1: 4. UFT is widely used with leucovorin as adjuvant chemotherapy in patients with colon cancer. As reported, UFT/leucovorin should not be taken simultaneously with food because a high fat content will reduce the systemic exposure to the active cytotoxic moiety of UFT. In this single-dose, randomized, two-way crossover study, we investigated the effects of a low-fat Japanese meal on the pharmacokinetics and oral bioavailability of UFT (2 x 100-mg capsules; dose in terms of tegafur) and leucovorin (1 x 25-mg tablet). METHODS:Patients (n = 12) were randomly assigned to receive both drugs after an overnight fast or 5 min after eating a standard Japanese breakfast (641 kcal), with a 3-day washout period between treatments. Pharmacokinetics (n = 12) were determined for tegafur, 5-fluorouracil, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin). RESULTS: For 5-fluorouracil pharmacokinetics, the maximum plasma concentration and the area under the curve were reduced by 73.7% and 47.4%, respectively, when UFT was taken postprandially, and the maximum plasma concentration and the area under the curve for uracil were reduced by 84.1% and 68.9%, respectively, compared with dosing on an empty stomach. These decreases in the systemic exposure to 5-fluorouracil were quite marked and may have an impact on its antitumor effect. CONCLUSION: A low-fat meal affects the pharmacokinetics of UFT similarly to a high-fat meal.
Authors: Barry C Lembersky; H Samuel Wieand; Nicholas J Petrelli; Michael J O'Connell; Linda H Colangelo; Roy E Smith; Thomas E Seay; Jeffrey K Giguere; M Ernest Marshall; Andrew D Jacobs; Lauren K Colman; Atilla Soran; Greg Yothers; Norman Wolmark Journal: J Clin Oncol Date: 2006-05-01 Impact factor: 44.544
Authors: B Damle; F Ravandi; S Kaul; D Sonnichsen; I Ferreira; D Brooks; D Stewart; D Alberts; R Pazdur Journal: Clin Cancer Res Date: 2001-03 Impact factor: 12.531
Authors: Jean-Yves Douillard; Paulo M Hoff; Jamey R Skillings; Peter Eisenberg; Neville Davidson; Peter Harper; Mark D Vincent; Barry C Lembersky; Seth Thompson; Antonella Maniero; Steven E Benner Journal: J Clin Oncol Date: 2002-09-01 Impact factor: 44.544
Authors: James Carmichael; Tadeusz Popiela; David Radstone; Stephen Falk; Markus Borner; Amit Oza; Torben Skovsgaard; Stephane Munier; Christophe Martin Journal: J Clin Oncol Date: 2002-09-01 Impact factor: 44.544