Disposition of a New, Nonsteroid, Antiandrogen, α,α,α-Trifluoro-2-methyl-4′-nitro-m-propionotoluidide (Flutamide), in Men Following a single Oral 200 mg Dose
A single oral 200 mg dose of tritiumlabeled α,α,α-trifluoro-2-methyl-4′-nitro-m-propionotoluidide (flutamide) was given to 3 men. Analysis of plasma, urine and feces shows flutamide is rapidly and completely absorbed and excreted mainly through the kidneys. Analysis of plasma radioactivity shows flutamide is rapidly and extensively metabolized—only 2.5% of plasma radioactivity 1 h after dosing is associated with flutamide. At least 10 other metabolites are present, of which 6 have been tentatively identified. These are α,α,α-trifluoro-4′-amino-m-acetotoluidide (A); α,α,α-trifluoro-4′-amino-2-methyl-m-lactotoluidide (B); α,α,α-trifluoro-4′-nitro-m-acetotoluidide (C); α,α,α-trifluoro-2-methyl-4′-nitro-m-lactotoluidide (D); α,α,α-trifluoro-4′-amino-2-methyl-m-propionotoluidide (E); and α,α,α-trifluoro-6-nitro-mtoluidine (F). (D) represents 23% of plasma tritium 1 h after drug and is a major metabolite at all other measured times. Each of the other metabolites accounts for <10% of plasma radioactivity. Minor amounts of flutamide and (A) through (F) are found in 0-24-h urine. An additional metabolite, α,α,α-trifluoro-2-amino-5-nitro-p-cresol, constitutes 25% of urine tritium.The rapid conversion of flutamide to (D) and the high plasma levels of (D) suggest (D) might be the active form of flutamide.