Following an oral dose of 14C-finasteride in
man, a mean of 39% ( range, 32-46% ) of the dose was excreted
in the urine in the form of metabolites; 57% ( range, 51-64%
) was excreted in the feces. The major compound isolated
from urine was the monocarboxylic acid metabolite; virtually
no unchanged drug was recovered. The t-butyl side chain
monohydroxylated metabolite has been isolated from plasma.
These metabolites possessed no more than 20% of the 5a-reductase
inhibitory activity of finasteride.
In a study in 15 healthy male subjects, the mean bioavailability
of finasteride 1-mg tablets was 65% ( range 26-170% ), based
on the ratio of AUC relative to a 5-mg intravenous dose
infused over 60 minutes. Following intravenous infusion,
mean plasma clearance was 165 mL/min ( range, 70-279 mL/min
) and mean steady-state volume of distribution was 76 liters
( range, 44-96 liters ). In a separate study, the bioavailability
of finasteride was not affected by food.
Approximately 90% of circulating finasteride is bound to plasma
proteins. Finasteride has been found to cross the blood-brain
barrier.
There is a slow accumulation phase for finasteride after
multiple dosing. At steady state following dosing with 1
mg/day, maximum finasteride plasma concentration averaged
9.2 ng/mL ( range, 4.9-13.7 ng/mL ) and was reached
1 to 2 hours postdose; AUC( 0-24 hr ) was 53 ng•hr/mL
( range, 20-154 ng•hr/mL ) and mean terminal half-life
of elimination was 4.8 hours ( range, 3.3-13.4 hours ).
Semen levels have been measured in 35 men taking finasteride
1 mg daily for 6 weeks. In 60% ( 21 of 35 ) of the samples,
finasteride levels were undetectable. The mean finasteride
level was 0.26 ng/mL and the highest level measured
was 1.52 ng/mL. Using this highest semen level measured
and assuming 100% absorption from a 5-mL ejaculate per day,
human exposure through vaginal absorption would be up to
7.6 ng per day, which is 750 times lower than the exposure
from the no-effect dose for developmental abnormalities
in Rhesus monkeys ( see PRECAUTIONS, Pregnancy ).
The elimination rate of finasteride decreases somewhat with age.
Mean terminal half-life is approximately 5-6 hours in men
18-60 years of age and 8 hours in men more than 70 years
of age. These findings are of no clinical significance,
and a reduction in dosage in the elderly is not warranted.
No dosage adjustment is necessary in patients with renal
insufficiency. In patients with chronic renal impairment
( creatinine clearance ranging from 9.0 to 55 mL/min
), the values for AUC, maximum plasma concentration, half-life,
and protein binding after a single dose of 14C-finasteride
were similar to those obtained in healthy volunteers. Urinary
excretion of metabolites was decreased in patients with
renal impairment. This decrease was associated with an increase
in fecal excretion of metabolites. Plasma concentrations
of metabolites were significantly higher in patients with
renal impairment ( based on a 60% increase in total radioactivity
AUC ). Furthermore, finasteride has been well tolerated
in men with normal renal function receiving up to 80 mg/day
for 12 weeks where exposure of these patients to metabolites
would presumably be much greater.
