Liquid Dutast USP- 30 ML

Dihydrotestosterone (DHT), a steroid hormone produced from testosterone by the enzyme 5-reductase is the primary active metabolite of testosterone (1). In male fetal development and puberty, it is essential for normal masculinization of the external genitalia and normal development of the prostate gland. In later life, DHT is associated with the development of benign prostatic hyperplasia (BPH) and androgenic alopecia. Users of testosterone based anabolic steroids are often at risk of developing disorders associated with excess DHT. These include BPH, scalp hair loss, hirsuitism (excess body hair, a particular problem for females) and acne. The enzyme 5-reductase is present throughout the body in two forms, type 1 and type 2 (2) Type 1 has been reported to be located predominantly in the skin, both in hair follicles and sebaceous glands, as well as in the liver, prostate, and kidney (3,4,5). Type 2 is found in the male genitalia and the prostate (6,7,8 ); recent research has also identified type 1 mRNA and enzyme activity in the prostate (9,10,11). The role of DHT in male fetal development was recognized when a deficiency of the type 2 5-reductase isoenzyme was described in association with a clinical syndrome characterized by male pseudohermaphroditism (12,13). These individuals are born with impaired masculinization of the external genitalia and a rudimentary prostate. In later life, they do not develop BPH or prostate cancer (14,15). This lack of development of BPH led to the development of an inhibitor of 5-reductase to treat this common condition (16) The first available 5-reductase inhibitor (finasteride) is selective for the type 2 isoenzyme (17). Its clinical utility in reducing enlarged prostates, relieving symptoms associated with BPH, and reducing the risk of associated complications has been documented in several clinical trials (18,19). More recently, 5-reductase inhibition has been proven effective in treating androgenetic alopecia (20). Finasteride suppresses serum DHT by about 70% (21).. However, as a selective type 2 isozyme inhibitor, finasteride has proved only moderately effective in treating BPH and more potent compounds are clearly needed. Dutasteride (GI-198745) is a dual inhibitor of 5alpha-reductase types 1 and 2 isozymes which appears to be suitable for use alone or in combination with alpha1-adrenoceptor antagonists for the treatment of BPH and associated symptoms. Dutasteride is a 6-azasteroid, which inhibits both type 1 and type 2 5-reductase isoenzymes. Several studies, conducted both by Glaxo, the developer of the drug, as well as independent studies, have demonstrated the efficacy and safety of dutasteride. In a randomized, double-blind, parallel group 4-week study sponsored by Glaxo, the developer of dutasteride, dutasteride (40 mg loading dose then 0.1, 0.5, 2.5 and 2.5 mg/day) was shown to more potently suppress dihydrotestosterone (DHT) as compared to finasteride (5 mg/d) in 53 subjects with benign prostatic hyperplasia. DHT was dose-dependently suppressed in dutasteride-treated subjects with a maximum suppression of 95% occurring with the 5 mg dose; 0.5 mg, the lowest maximally effective dose, decreased DHT levels by 90% at 4 weeks and by 94% at 24 weeks, while finasteride only suppressed levels by 67 and 76%, respectively. Although testosterone levels increased (9-27%) with DHT suppression with both agents, levels were considered normal. Similar incidence of adverse effects was observed for placebo and both treatment groups although decreased libido was observed in subjects given 5 mg finasteride or dutasteride. In an open-label, crossover study presented to the American Urology Association by Glaxo, 38 healthy male subjects were given the alpha-blocker tamsulosin (0.4 mg/day) or terazosin (titrated up to 10 mg/day) for 14 days, followed by 7-day washout and subsequent treatment with dutasteride (0.5 mg/day following a 40-mg loading dose) for 21 days, followed finally by a 14-day treatment with the combination of dutasteride plus tamoxifen or terazosin. The results showed no significant drug interactions as regards pharmacokinetics. In addition, the incidence of adverse events of headache, dizziness, musculoskeletal pain, orthostasis, nausea and emesis was lower when dutasteride was coadministered with tamoxifen (18% vs. 29%) or terazosin (35% vs. 67%) compared to either drug alone. As an example of an independent study, Clark et al reported that in their study a total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4