Effect of Gamiondam-tang (GMODT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (2) - Single Oral Combination Treatment of Tamoxifen 50 mg/kg with GMODT 100 mg/kg with 2.5 hr-intervals -

Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of GMODT with 2.5 hr-intervals. Methods : After 50 mg/kg of tamoxifen treatment, GMODT 100 mg/kg was administered with 2.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results : Two-half hr-interval co-administration with GMODT induced variable changes on the plasma tamoxifen concentrations as compared with tamoxifen single treated rats, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 (199.61%) and 1 hr (101.06%) after end of co-administration with GMODT, and also related significant (p<0.05) decreases of $t_{1/2}$ (-39.54%) and $MRT_{inf}$ (-43.94%) as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 50 mg/kg and GMODT 100 mg/kg with 2.5 hr-intervals, in this experiment. Conclusions : According to the results, GMODT critically decreased on the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Hence, the co-administration of GMODT and tamoxifen should be avoided in the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT on the breast cancer.