| Indication |
For the treatment of symptomatic benign prostatic hyperplasia
(BPH) in men with an enlarged prostate gland to improve symptoms, and
reduce the risk of acute urinary retention and the need for surgery. |
| Pharmacodynamics |
Dutasteride is a synthetic 4-azasteroid compound that is a
selective inhibitor of both the type 1 and type 2 isoforms of steroid 5
alpha-reductase (5AR), intracellular enzymes that convert testosterone
to 5 alpha-dihydrotestosterone (DHT). Type I 5a-reductase is predominant
in the sebaceous glands of most regions of skin, including scalp, and
liver. Type I 5a-reductase is responsible for approximately one-third of
circulating DHT. The Type II 5a-reductase isozyme is primarily found in
prostate, seminal vesicles, epididymides, and hair follicles as well as
liver, and is responsible for two-thirds of circulating DHT. |
| Mechanism of action |
Dutasteride inhibits the conversion of testosterone to 5
alpha-dihydrotestosterone (DHT), which is the androgen primarily
responsible for the initial development and subsequent enlargement of
the prostate gland. Testosterone is converted to DHT by the enzyme 5
alpha-reductase, which exists as 2 isoforms, type 1 and type 2.
Dutasteride is a competitive and specific inhibitor of both type 1 and
type 2 5 alpha-reductase isoenzymes, with which it forms a stable enzyme
complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor. |
| Absorption |
60% |
| Volume of distribution |
|
| Protein binding |
Highly bound to albumin (99%) and α-1 acid glycoprotein (96.6%). |
| Metabolism |
Hepatic. Extensively metabolized by CYP3A4 and CYP3A5 to active metabolites. |
| Route of elimination |
Dutasteride is extensively metabolized in humans. Dutasteride and its metabolites were excreted mainly in feces. |
| Half life |
5 weeks |
| Clearance |
Not Available |
| Toxicity |
Not Available |
