ABSENCE OF HEPATIC ENZYME-INDUCTION IN PROSTATE-CANCER PATIENTS RECEIVING CASODEX (BICALUTAMIDE)

The potential for hepatic enzyme induction by bicalutamide ('Casodex') was assessed in an open study in prostate cancer patients. A single, oral dose of antipyrine 1000 mg was given before and after 12 weeks' b icalutamide therapy [once daily 50 mg (n = 7) or 150 mg (n = 11)] and its pharmacokinetics and metabolism were determined. Plasma or saliva samples were taken for the measurement of antipyrine concentration. Ur ine samples were assayed for antipyrine and its three major metabolite s. With bicalutamide 50 mg, plasma antipyrine concentrations were maxi mal between 2 and 4h after administration, declined in a log-linear ma nner and were unaffected by bicalutamide therapy; with bicalutamide 15 0 mg, saliva antipyrine concentrations were maximal between 2 and 4 h, declined in a log-linear manner, and were also unaffected by bicaluta mide therapy. Antipyrine half-life was 16.3% shorter after bicalutamid e 50 mg (p < 0.05); a small decrease (13.5%) in half-life after bicalu tamide 150 mg was not statistically significant. A small reduction (18 .6%, p < 0.05) in the AUC(infinity) for antipyrine was noted after blc alutarnide 150 mg. A statistically significant reduction in antipyrine recovery was seen with the lower bicalutamide dose (23.7%, p<0.05). T he statistically significant changes were small in absolute terms and showed no dose-response relationship. Bicalutamide does not significan tly induce the hepatic enzymes responsible for antipyrine metabolism a nd has no obvious potential for producing clinically significant drug interactions due to enzyme induction.