Finasteride Half-Life: 5 to 6 Hours (What It Means)

What a 5 to 6 hour half-life means

Half-life is the time it takes for the plasma concentration of a drug to fall by half. For finasteride, the prescribing information gives a mean terminal half-life of about 5 to 6 hours in men 18 to 60 and about 8 hours in men over 70 [1]. Plasma levels peak 1 to 2 hours after a tablet [1].

Read alone, that number suggests a drug that is out of the body quickly. In plasma it largely is. But the plasma half-life measures the drug molecule, while the effect on DHT depends on an enzyme complex that turns over slowly [1]. A single 1 mg tablet suppresses serum DHT by 65% within 24 hours [1], and the label doses finasteride as one 1 mg tablet once daily, with or without meals [1].

Absorption, distribution and metabolism in numbers

Finasteride is about 65% bioavailable, and food does not change that [1]. It is about 90% bound to plasma proteins [1], and it crosses the blood-brain barrier [1].

The liver does the metabolic work, mainly through CYP3A4. Two metabolites have been identified, and neither has more than 20% of the activity of finasteride itself [1]. About 39% of a dose leaves in urine as metabolites and about 57% in feces [1].

Why DHT stays suppressed after the drug is gone

Finasteride is a competitive, specific inhibitor of type II 5-alpha reductase, the enzyme that converts testosterone to DHT. Type II is found mainly in the prostate, seminal vesicles, epididymides, hair follicles and liver, and accounts for about two-thirds of circulating DHT; type I accounts for the other third [1].

The label describes what happens at the enzyme: inhibition is accompanied by reduction of finasteride to dihydrofinasteride and formation of an adduct with NADP+, and the enzyme complex turns over slowly, with a half-life of about 30 days for type II and about 14 days for type I [1]. Because the enzyme complex turns over slowly, the effect on DHT outlasts the plasma half-life [1].

A pharmacokinetic review makes the same point from the other direction: a single dose of finasteride suppresses serum DHT for up to 4 days, longer than the terminal half-life of the drug would suggest [2].

The Propecia label says daily use for three months or more is usually necessary before benefit is observed, continued use is recommended to sustain benefit, and withdrawal of treatment leads to reversal of effect within 12 months [1].

HealthRX.com offers finasteride 1 mg by prescription.

How much DHT suppression different doses produce

A 42-day biopsy study enrolled 249 men with androgenetic alopecia and measured scalp and serum androgens before and after daily finasteride at 0.01, 0.05, 0.2, 1 or 5 mg, or placebo [3]. Scalp skin DHT fell 13.0% on placebo and by 14.9%, 61.6%, 56.5%, 64.1% and 69.4% at those doses, putting the 1 mg group at 64.1%. Serum DHT declined significantly by 49.5%, 68.6%, 71.4% and 72.2% at 0.05, 0.2, 1 and 5 mg (P<0.001) [3]. The authors concluded that doses as low as 0.2 mg per day maximally decreased both scalp and serum DHT [3].

Does the half-life change with age, kidney or liver problems?

Age shifts the number modestly: about 8 hours in men over 70 against 5 to 6 hours in younger men [1]. A pharmacokinetic review notes that terminal half-life values are higher in elderly men but that no dosage adjustment is needed [2]; the Proscar label likewise says no dosage adjustment is necessary in the elderly and that the decreased elimination rate in the elderly is of no clinical significance [6].

For renal impairment, the review explains that the metabolites which accumulate are relatively inactive and that more of the drug is excreted in feces in this setting [2], and the Proscar label says no dosage adjustment is necessary in patients with renal impairment [6].

Liver impairment is the open question. The review states that the effect of hepatic dysfunction on finasteride metabolism is unknown [2], and the Proscar label says the effect of hepatic impairment on finasteride pharmacokinetics has not been studied and that caution should be exercised in patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [6]. The review also reports slow accumulation with multiple doses despite the short half-life [2].

Trial results and postmarketing reports

Two 1-year placebo-controlled trials enrolled 1553 men aged 18 to 41 with male pattern hair loss, and 1215 of them continued in blinded extension studies for a second year [4]. Hair count in a 1-inch (5.1 cm2) circle of vertex scalp, starting from a baseline of 876 hairs, was 107 hairs higher than placebo at 1 year and 138 hairs higher at 2 years (P<0.001), while the placebo group kept losing hair [4]. Those are trial averages, not a forecast for an individual.

The Propecia label lists, among postmarketing reports, sexual dysfunction that continued after discontinuation of treatment, and describes these reports as voluntary, from a population of uncertain size, with a causal relationship that cannot reliably be established [1].