Kinetics of tamoxifen inhibition of aryl hydrocarbon hydroxylase activity of intestinal and hepatic microsomes from male rats.

The in vitro effects of tamoxifen on microsomal aryl hydrocarbon hydroxylase (AHH) activity from male rat liver and intestinal mucosa were examined. Tamoxifen inhibited microsomal activity from both liver and intestinal mucosa. Tamoxifen was a much more potent inhibitor of hepatic AHH activity as compared to its effects on intestinal AHH activity. At 0.50 mM, tamoxifen inhibited approximately 92% of AHH activity and only 7% of the intestinal activity. Kinetic studies demonstrated that the inhibition of hepatic AHH activity by tamoxifen at concentrations of 0.10 mM or less was non-competitive. However, the same tamoxifen concentrations gave an uncompetitive inhibition when intestinal microsomal AHH activity was studied. The data indicates that AHH inhibition by tamoxifen is both tissue and concentration dependent.