Dutasteride

Dutasteride belongs to a class of drugs called 5-alpha-reductase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT) . Finasteride also belongs to this group, but while dutasteride inhibits both isoforms of 5-alpha reductase, finasteride inhibits only one. Even so, a clinical study done by GlaxoSmithKline, the EPICS trial, did not find dutasteride to be more effective than finasteride in treating BPH. (In Vitro) :Dutasteride inhibits 3H-T conversion to 3H-DHT and, as anticipated, inhibits T-induced secretion of PSA and proliferation. However the drug also inhibited DHT-induced PSA secretion and cell proliferation (IC50 approximately 1 μM) .Dutasteride competes for binding the LNCaP cell AR with an IC50 approximately 1.5 μM. High concentrations of dutasteride (10-50 μM), but not finasteride, in steroid-free medium, resulted in enhanced cell death, possibly by apoptosis.Dutasteride reduces cell viability and cell proliferation in both cell lines tested (androgen-responsive (LNCaP) and androgen-unresponsive (DU145) human prostate cancer (PCa) ) . (In Vivo) :GG745 has a terminal half-life of approximately 240 hr, and single doses of >10 mg decreased DHT levels significantly more than did single 5-mg doses of finasteride.In placebo treated men without prostate cancer there was an 8.3% median increase in PSA at month 24 compared with -59.5% in those who received dutasteride, using doubled values to correct for dutasteride treatment.Toxicity: Dutasteride may affect male fertility and steroid hormone dynamics. Therefore, a 21-day reproduction study was conducted to determine the effects of dutasteride (10, 32 and 100 μg/L) on fish reproduction. Exposure to dutasteride significantly reduced fecundity of fish and affected several aspects of reproductive endocrine functions in both males and females.