Clinical pharmacokinetics and pharmacodynamics of finasteride.

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Steiner JF

Clinical pharmacokinetics and pharmacodynamics of finasteride.

Clin Pharmacokinet. 1996 Jan;30(1):16-27. doi: 10.2165/00003088-199630010-00002.

PubMed ID
8846625 [ View in PubMed
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Abstract

Finasteride is a potent 5 alpha-reductase inhibitor that has shown limited success in men treated for benign prostatic hyperplasia (success is defined as a decrease in the symptoms associated with urinary tract obstruction, and as increases in the urinary flow rate). 5 alpha-reductase is necessary for the prostatic conversion of testosterone to dihydrotesterone (DHT), the specific steroid that stimulates prostate transitional zone growth. Finasteride reduces the size of the prostate gland by 20%, but this does not correlate well with improvement in symptoms. Finasteride is well absorbed after oral administration and, while the rate of absorption may be slowed postprandially, the presence of food has no effect on the total bioavailability. Finasteride is widely distributed, but since its pharmacological effects are very specific to inhibition of 5 alpha-reductase, and since only the prostate gland, the scalp, and the genital skin contain high concentrations of this enzyme, few adverse reactions will be seen in other organ systems. Finasteride undergoes extensive hepatic metabolism to essentially inactive metabolites, which are eliminated through the bile and urine. The terminal elimination half-life (t1/2z) is 4.7 to 7.1 hours; but despite this, slow accumulation occurs with multiple doses. Values of t1/2z are higher in elderly men, but no dosage adjustments are necessary. Likewise, no dosage adjustments are necessary for patients with renal dysfunction, since the metabolites which accumulate are relatively inactive and well tolerated, and because greater faecal excretion of the metabolites occurs in these patients. The effect of hepatic dysfunction on the metabolism of finasteride is unknown. Therapeutic doses of finasteride produce a rapid and pronounced effect in reducing both plasma and prostate tissue levels of DHT. Doses below 0.5 mg/day do not produce much suppression of DHT levels, and doses above 5 mg/day have little additional benefit. A single dose of finasteride suppresses serum DHT levels for up to 4 days, longer than would be expected from the serum terminal elimination half-life (t1/2z) of the drug: this is probably due to the high affinity that finasteride has for the 5 alpha-reductase enzyme. Serum testosterone levels increase in patients receiving finasteride, but are not normally outside the upper limits of the normal range. Serum prostate-specific antigen (PSA) levels decrease with finasteride administration; the baseline for investigation of prostate cancer with elevated PSA levels should be one-half of the normal range. In responders to finasteride, the prostate gland shrinks in volume by about 20%, urinary flow rate improves by approximately 3 ml/s, and symptoms are relieved. The response to finasteride appears to be maximal at doses of 5 mg/day. For most men receiving finasteride, these effects will persist for at least the 5 years that long term studies have been conducted. Serum DHT levels increase again when finasteride therapy is discontinued, probably resulting in the return of the hyperplasia, decreased urine flow and obstructive symptoms. Finasteride is well tolerated, with loss of libido and sexual potency being the most commonly reported adverse reactions. No drug interactions with finasteride have been reported.

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