Indication |
For the treatment of symptomatic benign prostatic hyperplasia
(BPH) in men with an enlarged prostate to: Improve symptoms, reduce the
risk of acute urinary retention, reduce the risk of the need for surgery
including transurethral resection of the prostate. Also used for the
stimulation of regrowth of hair in men with mild to moderate
androgenetic alopecia (male pattern alopecia, hereditary alopecia,
common male baldness). |
Pharmacodynamics |
Finasteride is a synthetic 4-azasteroid compound. This drug is a
competitive and specific inhibitor of Type II 5a-reductase, an
intracellular enzyme that converts the androgen testosterone into
5α-dihydrotestosterone (DHT). Two distinct isozymes are found in mice,
rats, monkeys, and humans: Type I and II. Each of these isozymes is
differentially expressed in tissues and developmental stages. In humans,
Type I 5a-reductase is predominant in the sebaceous glands of most
regions of skin, including scalp, and liver. Type I 5a-reductase is
responsible for approximately one-third of circulating DHT. The Type II
5a-reductase isozyme is primarily found in prostate, seminal vesicles,
epididymides, and hair follicles as well as liver, and is responsible
for two-thirds of circulating DHT. Although finasteride is 100-fold more
selective for type II 5a-reductase than for the type I isoenzyme,
chronic treatment with this drug may have some effect on type I
5a-reductase. |
Mechanism of action |
The mechanism of action of Finasteride is based on its
preferential inhibition of Type II 5a-reductase through the formation of
a stable complex with the enzyme. Inhibition of Type II 5a-reductase
blocks the peripheral conversion of testosterone to DHT, resulting in
significant decreases in serum and tissue DHT concentrations, minimal to
moderate increase in serum testosterone concentrations, and substantial
increases in prostatic testosterone concetrations. As DHT appears to be
the principal androgen responsible for stimulation of prostatic growth,
a decrease in DHT concentrations will result in a decrease in prostatic
volume (approximately 20-30% after 6-24 months of continued therapy).
In men with androgenic alopecia, the mechanism of action has not been
fully determined, but finasteride has shown to decrease scalp DHT
concentration to the levels found in hairy scalp, reduce serum DHT,
increase hair regrowth, and slow hair loss. |
Absorption |
Not Available |
Volume of distribution |
|
Protein binding |
Approximately 90% |
Metabolism |
Drug is extensively metabolized, primarily in the liver via
CYP3A4. Two metabolites have been identified with ≤20% of the activity
of finasteride. |
Route of elimination |
Following an oral dose of 14C-finasteride in man (n = 6), a mean
of 39% (range, 32 to 46%) of the dose was excreted in the urine in the
form of metabolites; 57% (range, 51 to 64%) was excreted in the feces.
Urinary excretion of metabolites was decreased in patients with renal
impairment. This decrease was associated with an increase in fecal
excretion of metabolites. |
Half life |
4.5 hours (range 3.3-13.4 hours) |
Clearance |
- 165 mL/min [healthy young subjects]
|
Toxicity |
Not Available |