Percutaneous penetration and metabolism of topical flutamide in men.

[Άκης]

1: J Invest Dermatol. 1976 Jun;66(6):379-82. Links
Percutaneous penetration and metabolism of topical (14C)flutamide in men.
• Katchen B,
• Dancik S,
• Millington G.

This study was designed to determine the fate of the nonsteroid antiandrogen
flutamide in men following a single 6-hr topical application of 5 mg 14C-labeled
drug dissolved in 50% ethanol/50% propylene glycol. Analysis of 0-120 hr urine
shows at least 16% of the applied flutamide is absorbed. Fifty-six percent of the
dose is recovered from the site of application with cotton swabs moistened with
50% ethanol/50% propylene glycol. Flutamide plasma levels peak in 4 to 6 hr at
about 1.3 ng/ml and then decline rapidly to about 0.08 ng/ml 24 hr after
application. Only 13% of plasma 14C is associated with flutamide 6 hr after drug
application. There are at least 10 plasma metabolites, of which 6 have been
tentatively identified. These are alpha, alpha, alpha-trifluoro-4'-amino-macetotoluidide
(A); alpha, alpha, alpha-trifluoro-4'-amino-2-methyl-mlactotoluidide
(B); alpha, alpha, alpha-trifluoro-4'-nitro-m-acetotoluidide (C);
alpha, alpha, alpha-trifluoro-2-methyl-4'-nitro-m-lactotoluidide (D); alpha,
alpha, alpha-trifluoro-4'-amino-2-methyl-m-propionotoluidide (E); and alpha,
alpha, alpha-trifluoro-6-nitro-m-toluidine (F). (D) is the major plasma
metabolite, and its concentration exceeds flutamide's between 8 and 24 hr after
drug. All the plasma metabolites are found in 0-24 hr urine in minor amounts.
An additional metabolite, alpha, alpha, alpha-trifluoro-amino-5-nitro-p-cresol
(G), accounts for 27% of urine 14C.