Pharmacokinetic Changes of 5-Fluorouracil Absorption After a Subtotal Gastrectomy

Bae, Jae Moon; Jang, In Jin; Shin, Sang Goo; Han, Ho Seong; Kim, Hyong Lae; Kim, Young Woo; Park, Sung Soo

Abstract

5-fluorouracil(5-FU) and its derivatives have been prescribed preoperatively in Korea for oral administration to patients with gastric cancer as an adjuvant therapy. Since the conditions of the patients after gastrectomy may be different and thereby influence the absorption of 5-fluorouracil, we were interested in the pharmacokinetic changes of 5-fluorouracil absorption after gastric resection. Fourteen of 40 gastric cancer patients, who underwent radical subtotal gastrectomy with D2 lymphnode dissection for gastric cancer, were selected at Ewha Womans University Mok-Dong Hospital from May 1996 to December 1996. The plasma concentrations of 5-fluorouracil were determined before oral administration of 5-FU(500 mg/M2) at 15-min intervals for two hours, and then at 30-min intervals for two hours after oral administration during the pre- and the post-operative periods. High pressure liquid chromatography was used to determine the plasma concentrations of 5-FU. The pharmacokinetic indices included the area under the curve (AUC), the peak concentration (Cmax), and the time to peak concentration (Tmax). The mean postoperative AUC for 5-FU was 25.8+/-14.8% of the mean preoperative AUC, which was a significant decrease in the amount of 5-FU absorption postoperatively. The mean postoperative Cmax was 33.4+/-30.2% of the mean preoperative Cmax, which also meant a significant decrease of the peak concentration postoperatively. The Tmax of most patients were delayed postoperatively, but there was no significant change statistically. In conclusion, we found that the amount of absorbed 5-FU, as calculated by the AUC and the Cmax, significantly decreased after a subtotal gastrectomy by as much as 75 percent compared to the preoperation. Hence, it may be necessary to increase the dose of 5-FU after a subtotal gastrectomy by more than 75% of the preoperative dose. The subtotal gastrectomy did not have a significant effect on the absorptive velocity of 5-FU.