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Effects of bolus injection of 5-fluorouracil on steady-state plasma concentrations of 5-fluorouracil in Japanese patients with advanced colorectal cancer
Authors:Tamura Takao  Kuwahara Akiko  Kadoyama Kaori  Yamamori Motohiro  Nishiguchi Kohshi  Inokuma Tsubasa  Takemoto Yoshiji  Chayahara Naoko  Okuno Tatsuya  Miki Ikuya  Fujishima Yoshimi  Sakaeda Toshiyuki
Affiliation:Kinki University Nara Hospital, Nara 630-0293, Japan.
Abstract:Objectives: The irinotecan (CPT-11) + 5-fluorouracil (5-FU)/leucovorin (LV) + UFT/LV chemotherapy, in which repetitive oral administration of UFT/LV replaces the infusion of 5-FU/LV in the FOLFIRI regimen, has been proposed previously. In this study, five of 10 patients were injected with a bolus of 5-FU and the other were not injected with it in order to examine the effect of omitting it in terms of pharmacokinetics of 5-FU.Methods: The treatment consisted of the intravenous infusions of CPT-11 at 100 mg/m2 and l-LV at 15 mg/m2, and the injection of a bolus of 5-FU at 500 mg/m2 on day 1, and the repetitive oral administration of UFT/LV (300 mg/m2/day as tegafur + 75 mg/day of LV) on days 1-5. A total of 13 measurements of the plasma concentrations of uracil, 5-FU and tegafur were made per patient within 48 hr after the start of chemotherapy and the value of area under the concentration-time curve (AUC0-48) was evaluated. The plasma concentration was also determined at 2 weeks to assess long-term exposure to 5-FU.Results: The plasma concentrations of 5-FU at 24 hr after the start of treatment were 27.4 ng/mL and 9.4 ng/mL in the patients with and without the bolus injection, respectively. At 48 hr, they were 31.3 ng/mL and 10.4 ng/mL with the AUC0-48 values of 22.16 mg*h/L and 0.65 mg*h/L, respectively. The 5-FU was detected in the plasma at 226 hr after the last administration of UFT/LV for the patients with the bolus injection, but not for those without.Conclusion: A bolus of 5-FU on day 1 provided long-term exposure to 5-FU.
Keywords:5-fluorouracil   UFT   bolus injection   constant infusion   pharmacokinetics
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