Pharmacodynamics<unk>  is a 5α-reductase inhibitor. It is specifically a selective inhibitor of the type II and III isoforms of the enzyme. By inhibiting these two isozymes of 5α-reductase,<unk>  reduces the formation of the potent androgen dihydrotestosterone (DHT) from its precursor testosterone in certain tissues in the body such as the prostate gland, skin, and hair follicles. As such,<unk>  is a type of antiandrogen, or more specifically, an androgen synthesis inhibitor. However, some authors do not define<unk>  as an "antiandrogen," a term which can refer more specifically to antagonists of the androgen receptor.<unk>  results in a decrease of circulating DHT levels by about 65 to 70% with an oral dosage of 5 mg/day and of DHT levels in the prostate gland by up to 80 to 90% with an oral dosage of 1 or 5 mg/day. In parallel, circulating levels of testosterone increase by approximately 10%, while local concentrations of testosterone in the prostate gland increase by about 7-fold and local testosterone levels in hair follicles increase by around 27 to 53%. An oral dosage of<unk>  of only 0.2 mg/day has been found to achieve near-maximal suppression of DHT levels (68.6% for 0.2 mg/day relative to 72.2% for 5 mg/day).<unk>  does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with more than 100-fold less inhibitory potency for type I as compared to type II ( = 313 nM and 11 nM, respectively). This is in contrast to inhibitors of all three isoenzymes of 5α-reductase like dutasteride, which can reduce DHT levels in the entire body by more than 99%. In addition to inhibiting 5α-reductase,<unk>  has also been found to competitively inhibit 5β-reductase (AKR1D1). However, its affinity for the enzyme is substantially less than for 5α-reductase (an order of magnitude less than for 5α-reductase type I) and hence is unlikely to be of clinical significance. As of 2012, the tissues in which the different isozymes of 5α-reductase are expressed are not fully clear. This is because different investigators have obtained varying results with different reagents, methods, and tissues examined. However, the different isozymes of 5α-reductase appear to be widely expressed, with notable tissues including the prostate gland, seminal vesicles, testes, epididymides, skin, hair follicles, liver, kidneys, and brain, among others. By inhibiting 5α-reductase and thus preventing DHT production,<unk>  reduces androgen signaling in tissues like the prostate gland and the scalp. In the prostate, this reduces prostate volume, which improves BPH and reduces risk of prostate cancer.<unk>  reduces prostate volume by 20 to 30% in men with benign prostatic hyperplasia. Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis. Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from progesterone) activate the GABAA receptor in the brain; because<unk>  prevents the formation of neurosteroids, it functions as a neurosteroidogenesis inhibitor and may contribute to a reduction of GABAA activity. Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction. Pharmacokinetics The mean oral bioavailability of<unk>  is approximately 65%. The absorption of<unk>  is not affected by food. At steady-state with 1 mg/day<unk> , mean peak concentrations of<unk>  were 9.2 ng/mL (25 nmol/L). Conversely, following a single 5 mg dose of<unk> , mean peak levels of<unk>  were 37 ng/mL (99 nmol/L), and plasma concentrations increased by 47 to 54% following 2.5 weeks of continued daily administration. The volume of distribution of<unk>  is 76 L. Its plasma protein binding is 90%. The drug has been found to cross the blood–brain barrier, whereas levels in semen were found to be undetectable.<unk>  is extensively metabolized in the liver, first by hydroxylation via CYP3A4 and then by aldehyde dehydrogenase. It has two major metabolites, which are the tert-butyl side chain monohydroxylated and monocarboxylic acid metabolites. These metabolites show approximately 20% of the inhibitory activity of<unk>  on 5α-reductase. Hence, the metabolites of<unk>  are not particularly active. The drug has a terminal half-life of 5 to 6 hours in adult men (18–60 years of age) and a terminal half-life of 8 hours or more in elderly men (more than 70 years of age). It is eliminated as its metabolites 57% in the feces and 40% in the urine.
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