The pharmacokinetics of total radioactivity and unchanged drug were studied in patients receiving Anandron (Nilutamide, RU 23908) after a single dose of [14C] Anandron and after q12 h dosings of unlabelled drug for 2-7 weeks. The results indicate that the radioactivity in plasma consists of unchanged drug and metabolites. The plasma decay of Anandron after the absorption phase was biexponential in all patients, with the terminal phase half-life ranging from 23.3-87.2 h. The plasma decay of total radioactivity after the absorption phase was biexponential in 3/12 and monoexponential in 9/12 patients. The calculated terminal phase half-lives for total radioactivity after [14C] Anandron were 34.5-137.3 h. The AUC0-infinity of the unchanged drug in plasma represented 23%-38% of the AUC0-infinity of total radioactivity. Urinary radioactivity consisted primarily of metabolites, the majority of which were chloroform-nonextractable. Urinary excretion of radioactivity at 120 h ranged from 49%-78% of the administered dose; the unchanged Anandron (at 72 h) was 0.6%-1.3% of the dose. In three patients studied, the fecal excretion of Anandron was 1.4%-7.0%. Steady-state plasma levels (4.4-8.5 micrograms/ml) were attained within approximately 2 weeks from the initiation of twice daily dosing of Anandron. When the plasma pharmacokinetics of radioactivity and unchanged drug after the first single dose were compared with that during steady state, AUC0-12h of unchanged Anandron during steady state was significantly higher than the AUC0-infinity after the first single dose, suggesting that the plasma clearance of Anandron is lowered upon chronic administration of the drug, assuming that the bioavailability is constant.