COMPARATIVE PHARMACODYNAMIC ANALYSIS OF TAT-59 AND TAMOXIFEN IN RATS BEARING DMBA-INDUCED MAMMARY-CARCINOMA

TAT-59 suppressed the growth fo DMBA-induced mammary tumors in rats ea rlier and more strongly than tamoxifen (TAM). After oral administratio n of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and bl ood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day anti uterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the aff inity of the metabolites for estrogen receptors ranged from that of es tradiol to that of TAM. These results suggest that the superior anties trogenic activity of TAT-59 compared to TAM was either due to its high er penetration into tumor tissue or to the stronger antiestrogenic act ivity of its metabolites.