Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans.
The disposition of [14C]finasteride, a competitive inhibitor of steroid 5 alpha-reductase, was investigated after oral administration of 38.1 mg (18.4 microCi) of drug in six healthy volunteers. Plasma, urine, and feces were collected for 7 days and assayed for total radioactivity. Concentrations of finasteride and its neutral metabolite, omega-hydroxyfinasteride (monohydroxylated on the t-butyl side chain), in plasma and urine were determined by HPLC assay. Mean excretion of radioactivity equivalents in urine and feces equaled 39.1 +/- 4.7% and 56.8 +/- 5.0% of the dose, respectively. The mean peak plasma concentrations reached for total radioactivity (ng equivalents), finasteride, and omega-hydroxyfinasteride were 596.5 +/- 88.3, 313.8 +/- 99.4, and 73.7 +/- 11.8 ng/ml, respectively, at approximately 2 hr; the mean terminal half-life for drug and metabolite was 5.9 +/- 1.3 and 8.4 +/- 1.7 hr, respectively. Of the 24-hr plasma radioactivity, 40.9% was finasteride, 11.8% was the neutral metabolite, and 26.7% was characterized as an acidic fraction of radioactivity. Binding of [14C]finasteride to plasma protein was extensive (91.3 to 89.8%), with a trend suggesting concentration dependency (range 0.02 to 2 micrograms/ml). Little of the dose was excreted in urine as parent (0.04%) or omega-hydroxyfinasteride (0.4%). Urinary excretion of radioactivity was largely in the form of acidic metabolite(s)--18.4 +/- 1.7% of the dose was eliminated as the omega-monocarboxylic acid metabolite. Finasteride was scarcely excreted unchanged in feces. In humans, finasteride is extensively metabolized through oxidative pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Animal and Exploratory Drug Metabolism, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
J R
JR
Carlin
P
P
Höglund
L O
LO
Eriksson
P
P
Christofalo
S L
SL
Gregoire
A M
AM
Taylor
K E
KE
Andersson
D000284:Administration, Oral; D000328:Adult; D000736:Androstenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001378:Azasteroids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002250:Carbon Radioisotopes; D013196:Dihydrotestosterone / Q000097:blood; D005243:Feces / Q000737:chemistry; D018120:Finasteride; D006801:Humans; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000097:blood
D000736:Androstenes; D001378:Azasteroids; D002250:Carbon Radioisotopes; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride