Finasteride - How It Works
Clinical pharmacology details from the US FDA-approved label: how Finasteride works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action The development and enlargement of the prostate gland is dependent on the potent androgen, 5α -dihydrotestosterone (DHT). Type II 5α-reductase metabolizes testosterone to DHT in the prostate gland, liver and skin. DHT induces androgenic effects by binding to androgen receptors in the cell nuclei of these organs. Finasteride is a competitive and specific inhibitor of Type II 5α-reductase with which it slowly forms a stable enzyme complex. Turnover from this complex is extremely slow (t ½ ~ 30 days). This has been demonstrated both in vivo and in vitro . Finasteride has no affinity for the androgen receptor. In man, the 5α-reduced steroid metabolites in blood and urine are decreased after administration of finasteride.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The development and enlargement of the prostate gland is dependent on the potent androgen, 5α -dihydrotestosterone (DHT).
Type II 5α-reductase metabolizes testosterone to DHT in the prostate gland, liver and skin.
DHT induces androgenic effects by binding to androgen receptors in the cell nuclei of these organs.
Finasteride is a competitive and specific inhibitor of Type II 5α-reductase with which it slowly forms a stable enzyme complex.
Turnover from this complex is extremely slow (t ½ ~ 30 days).
This has been demonstrated both in vivo and in vitro .
Finasteride has no affinity for the androgen receptor.
In man, the 5α-reduced steroid metabolites in blood and urine are decreased after administration of finasteride.
12.2 Pharmacodynamics In man, a single 5-mg oral dose of finasteride tablets produces a rapid reduction in serum DHT concentration, with the maximum effect observed 8 hours after the first dose.
The suppression of DHT is maintained throughout the 24-hour dosing interval and with continued treatment.
Daily dosing of finasteride tablets at 5 mg/day for up to 4 years has been shown to reduce the serum DHT concentration by approximately 70%.
The median circulating level of testosterone increased by approximately 10 to 20% but remained within the physiologic range.
In a separate study in healthy men treated with finasteride 1 mg per day (n=82) or placebo (n=69), mean circulating levels of testosterone and estradiol were increased by approximately 15% as compared to baseline, but these remained within the physiologic range.
In patients receiving finasteride tablets 5 mg/day, increases of about 10% were observed in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but levels remained within the normal range.
In healthy volunteers, treatment with finasteride tablets did not alter the response of LH and FSH to gonadotropin-releasing hormone indicating that the hypothalamic-pituitary-testicular axis was not affected.
In patients with BPH, finasteride tablets have no effect on circulating levels of cortisol, prolactin, thyroid-stimulating hormone, or thyroxine.
No clinically meaningful effect was observed on the plasma lipid profile (i.e., total cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) or bone mineral density.
Adult males with genetically inherited Type II 5α -reductase deficiency also have decreased levels of DHT.
Except for the associated urogenital defects present at birth, no other clinical abnormalities related to Type II 5α -reductase deficiency have been observed in these individuals.
These individuals have a small prostate gland throughout life and do not develop BPH.
Pharmacokinetics
12.3 Pharmacokinetics Absorption In a study of 15 healthy young subjects, the mean bioavailability of finasteride 5-mg tablets was 63% (range 34 to 108%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. Maximum finasteride plasma concentration averaged 37 ng/mL (range, 27 to 49 ng/mL) and was reached 1 to 2 hours postdose. Bioavailability of finasteride was not affected by food. Distribution Mean steady-state volume of distribution was 76 liters (range, 44 to 96 liters). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing. After dosing with 5 mg/day of finasteride for 17 days, plasma concentrations of finasteride were 47 and 54% higher than after the first dose in men 45 to 60 years old (n=12) and ≥70 years old (n=12), respectively. Mean trough concentrations after 17 days of dosing were 6.2 ng/mL (range, 2.4 to 9.8 ng/mL) and 8.1 ng/mL (range, 1.8 to 19.7 ng/mL), respectively, in the two age groups. Although steady state was not reached in this study, mean trough plasma concentration in another study in patients with BPH (mean age, 65 years) receiving 5 mg/day was 9.4 ng/mL (range, 7.1 to 13.3 ng/mL; n=22) after over a year of dosing. Finasteride has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF. In 2 studies of healthy subjects (n=69) receiving finasteride tablets 5 mg/day fo