Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 1:4 tegafur and uracil combination

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, were examined in 26 patients with macroscopic Stage I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28 +/- 26.88, 4.41 +/- 1.78, and 0.51 +/- 0.20 micrograms h ml-1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.