Finasteride (finasteride)

Finasteride is a competitive and specific inhibitor of Type II 5alpha-reductase, an intracellular enzyme that convertstestosteroneto 5alpha-dihydrotestosterone (DHT).

Finasteride is a synthetic 4-azasteroid compound. The drug is a specific, competitive inhibitor of steroid type II 5alpha-reductase, an intracellular enzyme present in high concentrations in the liver, skin, and prostate gland. The conversion of testosterone to the active metabolite 5alpha-dihydrotestosterone (DHT) depends on the presence of this enzyme.

5alpha-Reductase is present as 2 distinct isoenzymes, type I and type II, in humans and certain animals. Type I 5alpha-reductase is found principally in the sebaceous and sweat glands of the skin, including scalp, follicular and epidermal keratinocytes, and dermal papilla cells, and also in the liver; this isoenzyme is responsible for approximately one-third of circulating DHT. The Type II isoenzyme is found predominantly in the prostate, seminal vesicles, epididymides, and liver, and is detectable in the inner root sheath of hair follicles and epidermal keratinocytes; this isoenzyme is responsible for two-thirds of circulating DHT.

Although testosterone is the principal circulating androgen, conversion to DHT amplifies the androgenic effect in androgen-sensitive target tissues such as the skin and scalp.

In men with androgenetic hair loss, increased amounts of DHT and 5alpha-reductase lead to miniaturized hair follicles and a shortened hair growth cycle; these alterations are not seen in hairy scalp portions of men with androgenetic hair loss or in patients without alopecia. Evidence that testosterone (and DHT) and steroid 5alpha-reductase may be involved in androgenetic hair loss comes from clinical observations in men with congenital 5alpha-reductase deficiency and in hypogonadal men. Androgenetic hair loss is not observed in these men, and hair loss in hypogonadal men can be induced by administration of testosterone.

In men with congenital 5alpha-reductase deficiency (pseudohermaphroditism), the gene for type II 5alpha-reductase activity is defective, while the gene for type I isoenzyme activity remains unaffected. These data suggest that while the Type II isoenzyme is not as prevalent in human scalp as the Type I isoenzyme, the Type II isoenzyme is involved in the development of androgenetic alopecia.

The exact mechanism of action of finasteride in patients with androgenetic alopecia has not been fully elucidated since the role of 5alpha-reductase and DHT in male-pattern baldness has not been fully elucidated. In vitro binding studies indicate that finasteride inhibits Type II 5alpha-reductase by binding tightly to the enzyme and is 100-fold more selective for this isoenzyme than for the Type I isoenzyme. Inhibition of 5alpha-reductase by finasteride is accompanied by reduction of finasteride to dihydrofinasteride and adduct formation with nicotinamide adenine dinucleotide phosphate (NADP+).

This enzyme complex has a slow rate of turnover in the body (half-life of about 30 days for the Type II isoenzyme complex and 14 days for the Type I complex). Although in vitro studies suggest that finasteride acts principally through Type II 5alpha-reductase, some clinicians suggest that chronic treatment with finasteride also may have some effect on the Type I isoenzyme.

Inhibition of Type II 5alpha-reductase by finasteride blocks the peripheral conversion of testosterone to DHT, resulting in substantial reductions in serum and tissue DHT concentrations. In men with androgenetic alopecia, high-dose oral finasteride (5 mg) decreases scalp DHT concentrations to levels found in hairy scalp, reduces serum DHT, increases hair regrowth, and slows hair loss. Finasteride may affect scalp hair growth through reductions in local and systemic DHT because the scalp is highly vascularized; the relative contributions of reductions in serum and scalp concentrations to the observed increase in scalp hair has not been elucidated.

Finasteride has no affinity for the androgen receptor and has no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational effects.

The mean bioavailability of finasteride 1-mg tablets is 65%. At steady-state dosing, peak plasma concentrations were reached in 1 to 2 hours post-dose. The bioavailability of finasteride is not affected by food.

Approximately 90% of circulating finasteride is bound to plasma proteins. The drug crosses the blood-brain barrier. Finasteride is extensively metabolized in the liver, primarily via cytochrome P-450(CYP) enzymes.

The 2 metabolites that have been identified (t-butyl side chain monohydroxylated andmonocarboxylic acid) exhibit no more than 20%of the 5alpha-reductase inhibitory activity of the parent drug. The mean terminal half-life of finasteride is approximately 5-6 hours in men 18-60 years of age and 8 hours in men >70 years of age. Following administration of an oral dose, approximately 39% of the dose is excreted in urine in the form of metabolites and 57% is excreted in feces.

USES: This medication is used to treat male pattern baldness (androgenetic alopecia) at the crown and in the middle of the scalp. It should be used by adult men only. This medication works by decreasing the amount of a natural body hormone (DHT).

Decreasing the amount of DHT leads to increased hair regrowth and slower hair loss. Hair growth on other parts of the body is not affected by finasteride. Women and children should not use this medication.

Generic name: finasteride
Pronunciation: (fin-AST-er-ide)

The following indications are listed for Finasteride:

• Male Patterned Baldness

Also known as: Alopecia Hereditaria In Men, Androgenetic Alopecia, Hereditary Alopecia In Males, Male Pattern Alopecia.

No ICD codes are available for this drug.