Dutasteride

Systematic (IUPAC) name
(5a, 17ß)-N-{2,5 bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide
Identifiers
CAS number	164656-23-9
ATC code	G04CB02
PubChem	CID 6918296
DrugBank	APRD00385
ChemSpider	5293502
Chemical data
Formula	C27H30F6N2O2
Mol. mass	528.53 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	60%
Protein binding	99%
Metabolism	Hepatic (CYP3A4-mediated)
Half-life	5 weeks
Excretion	Fecal
Therapeutic considerations
Pregnancy cat.	X(US) Not to be handled by pregnant women
Legal status	POM (UK) ?-only (US)
Routes	Oral
Y(what is this?)  (verify)

Dutasteride (brand name Avodart) is a 5-alpha-reductase inhibitor that inhibits the conversion of testosterone into dihydrotestosterone (DHT). It is approved for the treatment of benign prostatic hyperplasia (BPH) and is prescibed off-label for the treatment of male pattern baldness (MPB). Avodart is manufactured and marketed by GlaxoSmithKline.

[edit] Classification and method of action

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, which is also approved for the treatment of benign prostatic hyperplasia (BPH), in addition to the treatment of male pattern baldness (MPB), belongs to this group of drugs. Dutasteride inhibits both isoforms of 5-alpha reductase, Type I and Type II, whereas finasteride only inhibits Type II. There are no long-term randomized trials comparing the effects of dutasteride and finasteride in patients with BPH. The EPICS trial, a 12-month clinical study done by GlaxoSmithKline, demonstrated treatment with dutasteride and finasteride resulted in similar decreases in prostate volume, with numerically but not statistically significantly greater improvements in symptom scores for the dutasteride group.^[1] Finasteride is marketed by Merck under the trademark names Proscar (5 mg/day finasteride) for BPH and Propecia (1 mg/day finasteride) for MPB. Published data from controlled clinical trials demonstrated that 5 mg finasteride did not have better results than 1 mg for the treatment of MPB.^[2]

[edit] Uses

While dutasteride is only officially approved to treat enlargement of the prostate gland (at a dose of 0.5 mg/day),^[3] phase I and II clinical trials for dutasteride as a hair loss drug were also undertaken, but called off in late 2002. The reason the trials were called off is not publicly known. Industry sources speculate that Avodart would have been seen as too similar to Propecia (1 mg/day finasteride) to have proven itself profitable on the market as a hair loss treatment. However, phase II results indicated that dutasteride at both 0.5 mg and 2.5 mg/day generated a superior hair count to finasteride 5 mg at 12 and 24 weeks.^[4]

In a test area at 24 weeks, results showed:^[5]

Placebo - Minus 32.3 hairs

Finasteride 5 mg - 75.6 hairs

Dutasteride 0.1 mg - 78.5 hairs

Dutasteride 0.5 mg - 94.6 hairs

Dutasteride 2.5 mg - 109.6 hairs

In December 2006, GlaxoSmithKline started a new Phase III, six month study in Korea to test the safety, tolerability and effectiveness of a once-daily dose of dutasteride (0.5 mg) for the treatment of MPB in the vertex region of the scalp (types IIIv, IV and V on the Hamilton-Norwood scale). The study has been completed as of January 2009.^[6] The future impact that this study will have on the approval or disapproval by the U.S. Food and Drug Administration (FDA) of Avodart for the treatment of MPB in the United States is yet to be determined.

The REDUCE trial, a randomized controlled trial of 6,729 men comparing dutasteride to placebo for prevention of prostate cancer, found an overall reduction of 22% in the incidence of prostate cancer over 4 years. However, the reduction was entirely in Gleason grades 5 and 6 cancers, which are less life-threatening and often not treated. In Gleason grade 7-10, which are life-threatening, there was no reduction in cancer.^[7] According to an editorial, "Dutasteride and finasteride do not prevent prostate cancer but merely temporarily shrink tumors that have a low potential for being lethal." They may also delay diagnosis until prostate cancer is difficult to cure.^[8]

[edit] Side effects

Avodart 500 micrograms soft capsules (AU)

Adverse events^[9]

Year 1

Placebo (n = 2158)

Impotence 3% - Decreased libido 2% - Ejaculation disorders <1% - Breast Disorders <1%

Avodart (n = 2167)

Impotence 6% - Decreased libido 4% - Ejaculation disorders 2% - Breast Disorders 1%

Year 2

Placebo (n = 1736 )

Impotence 1% - Decreased libido <1% - Ejaculation disorders <1% - Breast Disorders <1%

Avodart (n = 1744)

Impotence 2% - Decreased libido <1% - Ejaculation disorders <1% - Breast Disorders 1%

[edit] Teratogenic effect

The teratogenic effect from dutasteride is harmful to male children. Women who are pregnant should not handle the capsules, as inadvertent consumption could cause birth defects of the male fetus. The adverse effects would be similar to 5-alpha-reductase deficiency, where a developing male child is naturally deficient in 5-alpha reductase Type II, and thus unable to synthesize it. As dutasteride blocks the same process, developing males would have a DHT deficiency with its adverse effects as a result of the drug. Men should not donate blood while taking Avodart and for at least 6 months after treatment ends. Avodart can be carried in the blood and could cause birth defects if a pregnant women receives a transfusion with blood that contains dutasteride.^[10]

[edit] Synthesis

Batchelor, K. W.; Frye, S. V.; Dorsey, G. F.; Mook, R. A.; 1996, U.S. Patent 5,565,467.

[edit] See also

• Finasteride
• Dihydrotestosterone
• Baldness treatments
• Male pattern baldness
• Benign prostatic hyperplasia

[edit] External links

• Avodart | Official Website

[edit] References

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Dutasteride".