Propecia Mechanism of Action

5-Alpha Reductase Inhibitor (For Male Pattern Baldness).
Pharmacology: Pharmacodynamics: Finasteride had no effect on circulating levels of cortisol, thyroid-stimulating hormone, or thyroxine, nor did it affect the plasma lipid profile (e.g., total cholesterol, low density lipoproteins, high density lipoproteins, and triglycerides) or bone mineral density. In studies with finasteride, no clinically meaningful changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol or prolactin were detected. Gonadotropin-releasing hormone (GnRH) stimulated levels of LH or FSH were not altered, indicating that regulatory control of the hypothalamic-pituitary-testicular axis was not affected. Circulating levels of testosterone were increased by approximately 10-15% compared with placebo, yet remained within the physiologic range. There was no effect on semen parameters in men treated with finasteride 1 mg/day for 48 weeks.
Finasteride appeared to inhibit both C₁₉ and C₂₁ steroid metabolism and hence appeared to have an inhibitory effect on both hepatic and peripheral Type II 5α-reductase activity. The serum DHT metabolites androstenediol glucuronide and androsterone glucuronide were also significantly reduced. This metabolic pattern is similar to that observed in individuals with a genetic deficiency of Type II 5α-reductase who have markedly decreased levels of DHT and who do not suffer from male pattern hair loss.
Pharmacokinetics: Absorption: Relative to an intravenous reference dose, the oral bioavailability of finasteride is approximately 80%. The bioavailability is not affected by food. Maximum finasteride plasma concentrations are reached approximately two hours after dosing and the absorption is complete after 6-8 hours.
Distribution: Protein binding is approximately 93%. The volume of distribution of finasteride is approximately 76 liters.
There is modest accumulation of finasteride in plasma after multiple dosing. At steady state following dosing with 1 mg/day, maximum finasteride plasma concentration averaged 9.2 ng/mL and was reached 1 to 2 hours postdose; AUC_{(0-24 hr)} was 53 ng·hr/mL.
Finasteride has been recovered in the cerebrospinal fluid (CSF) but the drug does not appear to concentrate preferentially to the CSF. A very small amount of finasteride has also been detected in the seminal fluid of subjects receiving finasteride.
Metabolism: Finasteride is metabolized primarily via the cytochrome P450 3A4 enzyme subfamily. Following an oral dose of ¹⁴C-finasteride in man, two metabolites of finasteride were identified that possess only a small fraction of the 5α-reductase inhibitory activity of finasteride.
Elimination: Following an oral dose of ¹⁴C-finasteride in man, 39% of the dose was excreted in the urine in the form of metabolites (virtually no unchanged drug was excreted in the urine) and 57% of total dose was excreted in the feces.
Plasma clearance is approximately 165 mL/min.
The elimination rate of finasteride decreases somewhat with age. Mean terminal half-life is approximately 5-6 hours in men 18-60 years of age and 8 hours in men more than 70 years of age. These findings are of no clinical significance and hence, a reduction in dosage in the elderly is not warranted.
Characteristics in Patients: In patients with chronic renal impairment whose creatinine clearance ranged from 9 to 55 mL/min, the disposition of a single dose of ¹⁴C-finasteride was not different from that in healthy volunteers. Protein binding also did not differ in patients with renal impairment. A portion of the metabolites that normally is excreted renally was excreted in the feces. It therefore appears that fecal excretion increases commensurate to the decrease in urinary excretion of metabolites. No adjustment in dosage is necessary in nondialyzed patients with renal impairment.