Emi Yasunori, Sumiyoshi Yasushi, Oki Eiji, Kakeji Yoshihiro, Fukui Yousuke, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Fukuoka Igaku Zasshi. 2007 Dec;98(12):418-24.
Gamma-hydroxybutylic acid (GHB) and gamma-butyrolactone (GBL), the metabolites of UFT, which is an oral fluoropyrimidine, have been reported to inhibit angiogenesis with IC50 values of 25.8 ng/ml. The pharmacokinetics of GHB and GBL were examined after the administration of UFT in patients with gastric cancer. The patients received 200 mg of UFT orally twice a day. Peripheral blood samples were collected at 0, 0.5, 1, 2 and 4 hr after the time of dosing on day 5. The baseline and endogenous GBL concentrations in plasma were 20.2 +/- 7.5 ng/ml for patients and 16.8 +/- 4.0 ng/ml for volunteers (P = 0.221). The values of C(max) for tegafur, uracil, 5-FU and GBL were 14.7 +/- 5.2 and 4.0 +/- 2.8 microg/ml, 191.2 +/- 115.3 and 147.5 +/- 57.3 ng/ml, respectively, and the values of Tmax were 1.0 +/- 0.6, 1.1 +/- 0.6, 0.9 +/- 0.6 and 1.2 +/- 0. 6 hr, respectively. The concentration of GBL was much higher than its IC50 value for angiogenesis. GBL is thus suggested to contribute to the anticancer effects of UFT in addition to that of 5-FU, which is continuously metabolized from UFT.
