PHARMACOKINETICS AND BIOAVAILABILITY OF TAMOXIFEN IN POSTMENOPAUSAL HEALTHY WOMEN

A randomised cross-over study in 24 postmenopausal women was selected to establish bioequivalence of two tamoxifen (CAS 10540-29-1) formulat ions. In addition, this study compiled pharmacokinetic parameters for the current 30 mg regimen in postmenopausal women, the target populati on of tamoxifen therapy. Mean C-max values of 59.1 +/- 8.9 (T) and 63. 6 +/- 11.1 (R) ng/ml were attained 3.6 +/- 1.2 (T) and 3.2 +/- 1.1 (R) h after administration of 30 mg tamoxifen for the test (T) and the re ference (R) formulation. The mean AUC((0-480)) of tamoxifen was calcul ated as 3299.7 +/- 761.2 (T) and 3370.1 +/- 701.9 (R) ng x h/ml. The c orresponding AUC((0-480)) of the active metabolite, N-desmethyl-tamoxi fen, exceeded that of the parent drug with 4359.7 +/- 830.5 (T) and 43 06.3 +/- 835.2 (R) ng x h/ml, whereas maximal concentrations of the me tabolite were distinctly decreased with 14.4 +/- 3.3 (T) und 14.3 +/- 2.4 (R) ng/ml. The pharmacokinetic parameters evaluated in this study are well in line with already known pharmacokinetic data generated wit h young male volunteers and postmenopausal patients with breast cancer . Precise analytics and an extremely long blood sampling period facili tated an accurate determination of tamoxifen's half-life in postmenopa usal women with 210.1 +/- 60.8 (T) und 209.8 +/- 59.9 (R) h. Based on the extremely long half-life, the suitability of a cross-over design i s discussed and recommended for further studies.