Effect of toremifene on antipyrine elimination in the isolated perfused rat liver

Abstract

Toremifene is a triphenylethylene antioestrogen with significant antitumour activity. It is structurally very similar to tamoxifen. Both drugs undergo extensive hepatic metabolism and tamoxifen is known to inhibit hepatic mixed-function oxidases (MFO). Using the isolated perfused rat-liver model, we investigated the effect of toremifene on the elimination of antipyrine, a standard marker of MFO activity. Perfusate consisted of 20% red cells in a modified Krebs-Henseleit buffer, and 80 ml was recirculated at 14 ml/min for 3 h. High but clinically relevant steady-state toremifene levels of 3 and 10 μg/ml were achieved using bolus plus constant infusion into the reservoir. Elimination of 2.5 mg..