Hormones 2016

Finasteride
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 5-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
(drugbank, 2013d).
Pharmacokinetics
Finasteride is variably absorbed following oral administration, with a mean
bioavailability of about 63% (RxList, 2014), peak plasma concentrations are
achieved 1-2 hours after taking an oral dose. It is metabolised in the liver,
and excreted in the urine and faeces as its metabolites. The mean half- life
is 6 hours in patients less than 60 years, but may be prolonged to about 8
hours in patients older than 70 years (TGC, 2015a), and in some patients
up to about 15 hours (RxList, 2014). 39% excreted in the urine, and 57%
excreted in the faeces (RxList, 2014), and it is also excreted in the semen
(BNF, 2016a).
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 faeces. Urinary excretion of metabolites was decreased in patients
with renal impairment. This decrease was associated with an increase
in faecal excretion of metabolites.
Half life - 4.5 hours (range 3.3-13.4 hours)
Clearance - 165 mL/min [healthy young subjects] (drugbank, 2013d).
Typical dosage
Pre-op - 0.05–1 mg/day
Post-op - 0.05–1 mg/day (unknown, 2005).
Route
Oral - Tablets - Proscar, Propecia.
121
Version 2016.3576– – Document LATEXed – 1st May 2016
[git] • Branch: 1.5 @ 26b5e6d • Release: 1.5 (2016-05-01)