Pharmacodynamics

Finasteride, a synthetic 4- azasteroid compound, is a specific inhibitor of 5 alpha- reductase, an intracellular enzyme that converts androgenic testosterone into 5alpha-dihydrotestosterone (DHT). Administration of finasteride 1 mg decreases scalp and serum DHT concentration, increased amounts of which are thought to be responsible for male pattern hair loss (androgenetic alopecia).

Pharmacokinetics

Absorption

In a study in 15 healthy young male subjects, the mean bioavailability of finasteride

1 mg tablets was 65% (range: 26–170%), based on the ratio of area under the curve (AUC) relative to an intravenous reference dose. At steady state following dosing with 1 mg/day (n=12), maximum finasteride plasma concentration averaged 9.2 ng/mL (range: 4.9–13.7 ng/mL) and was reached 1 to 2 hours post-dose. Bioavailability of finasteride was not affected by food.

Distribution

Mean steady-state volume of distribution was 76 litres (range: 44–96 litres; n=15). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing.

Finasteride has been found to cross the blood-brain barrier.

Semen levels have been measured in 35 men taking finasteride 1 mg/day for 6 weeks and in 60% (21 of 35) of the samples, finasteride levels were undetectable (<0.2 ng/mL). The mean finasteride level was 0.26 ng/mL and the highest level measured was 1.52 ng/mL. Using the 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 and 650-fold less than the dose of finasteride (5 μg), which had no effect on circulating DHT levels in men.

Metabolism

Finasteride is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5alpha-reductase inhibitory activity of finasteride.

Excretion

Following an oral dose of 14 C-finasteride in men (n=6), 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 faeces.

Mean terminal half-life is approximately 5 to 6 hours in men, 18 to 60 years of age, and 8 hours in men more than 70 years of age.