dutasteride

デュタステリド

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/24 14:56:31」(JST)

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Dutasteride

Systematic (IUPAC) name
(5α, 17β)-N-{2,5 bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide
Clinical data
Trade names	Avodart
AHFS/Drugs.com	monograph
MedlinePlus	a603001
Pregnancy cat.	X (US) Not to be handled by pregnant women
Legal status	POM (UK) ℞-only (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	60%
Protein binding	99%
Metabolism	Hepatic (CYP3A4-mediated)
Half-life	5 weeks
Excretion	Fecal
Identifiers
CAS number	164656-23-9 Y
ATC code	G04CB02
PubChem	CID 6918296
DrugBank	DB01126
ChemSpider	5293502 Y
UNII	O0J6XJN02I Y
KEGG	D03820 Y
ChEBI	CHEBI:521033 Y
ChEMBL	CHEMBL1200969 N
Chemical data
Formula	C27H30F6N2O2
Mol. mass	528.53 g/mol
SMILES FC(F)(F)c1cc(c(cc1)C(F)(F)F)NC(=O)[C@@H]3[C@]2(CC[C@H]4[C@H]([C@@H]2CC3)CC[C@H]5NC(=O)\C=C/[C@]45C)C
InChI InChI=1S/C27H30F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,10,12-13,15-17,19,21H,4,6-9,11H2,1-2H3,(H,34,37)(H,35,36)/t15-,16-,17-,19+,21+,24-,25+/m0/s1 Y Key:JWJOTENAMICLJG-QWBYCMEYSA-N Y
N (what is this?)  (verify)

Dutasteride (trademark name Avodart, manufactured by GlaxoSmithKline) is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone (DHT).

Dutasteride is approved by the Food and Drug Administration (FDA) for treatment of benign prostatic hyperplasia (BPH) and prescribed off-label for treatment of male pattern baldness (MPB).

Medical uses

Benign prostatic hyperplasia

Dutasteride is approved for the treatment of benign prostatic hyperplasia (BPH); colloquially known as an "enlarged prostate".

Male pattern baldness

Phase I and II clinical trials for dutasteride as a hair loss drug were undertaken, but called off in late 2002, with reasons for termination unreported.

The 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.

In the phase II trials, an expert panel observing a one-inch diameter circle on the vertex of the head reported the following results at 24 weeks:

• Placebo: - 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 launched 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 male pattern baldness (MPB) in the vertex region of the scalp (types IIIV, IV and V on the Hamilton-Norwood scale). The study was completed in January 2009. Future intentions by GlaxoSmithKline to continue or abandon plans for FDA approval of dutasteride in treatment of MPB remain unknown.

Contraindications

Causes birth defects in male embryos and fetuses, but not in female. Dutasteride has teratogenic effects in male fetuses. It causes abnormalities of physiological development if during gestation a pregnant woman is exposed to dutasteride. Women who are pregnant should not handle the capsules since dutasteride is absorbed through the skin.

The adverse effects of dutasteride are identical 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 inactivates 5-alpha reductase type II developing males would have the same adverse effects as a result of the drug as they would have with the deficiency.

Men who are taking dutasteride should not donate blood, and due to its long half-life, should also not donate blood for at least 6 months after the cessation of treatment. These precautions are to be taken in order to prevent the potential risk of causing birth defects in a pregnant woman who receives a transfusion with blood that contains dutasteride.

Adverse effects

Clinical trial results

	Impotence	Decreased libido	Ejaculation disorders	Breast disorders
Month 0-6 ( n = 2,167 )	4.7%	3%	1.4%	0.5%
Month 7-12 ( n = 1,901 )	1.4%	0.3%	0.5%	1.1%
Month 13-18 ( n = 1,725 )	1%	0.1%	0.4%	0.8%
Month 19-24 ( n = 1,605 )	0.8%	0.3%	0.1%	0.6%

Observed in practice

The FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer. While the potential for positive, negative or neutral changes to the potential risk of developing prostate cancer with dutasteride has not been established, evidence has suggested it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer. The primary area for concern is for patients who may develop prostate cancer whilst taking dutasteride for benign prostatic hyperplasia, which in turn could delay diagnosis and early treatment of the prostate cancer, thereby potentially increasing the risk of these patients developing high-grade prostate cancer.

Mechanism 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).

Dutasteride versus Finasteride

Finasteride, is also approved for the treatment of benign prostatic hyperplasia, or BPH. In distinction to dutasteride, it has also currently has formal FDA approval for the treatment of male pattern baldness (MPB). The medications belong to the same class of drugs. Dutasteride inhibits two of the three isoforms of 5-alpha reductase, I and II, whereas finasteride only inhibits type II, and has a much shorter half-life.

Drug related adverse events have been reported to be similar in comparisons of dutasteride and finasteride in BPH in a randomized clinical trial done by GlaxoSmithKline. According to the study:

No significant differences from placebo were observed for any of the treatment groups [comparing finasteride and dutasteride], except for an increased reporting of serious adverse events with 0.01 mg dutasteride. None of the serious adverse events were considered by the investigators to be drug related. The most common adverse events (occurring in 15% or more of patients in at least one treatment group) were: ear, nose, and throat infections; malaise and fatigue; headaches;altered libido; musculoskeletal pain; erectile dysfunction; and dizziness. There were no significant differences in the reporting of the most common adverse events between the active treatment groups and the placebo group apart from the increased reporting of altered libido in the highest dose dutasteride group (5 mg) and the finasteride group, which both had similar reporting rates.

This confirmed findings of earlier studies in patients with BPH, comparing the 5 mg dose of finasteride to the 0.5 mg dose of dutasteride. The EPICS trial, a 12-month clinical study also 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. Finasteride is marketed by Merck under trademark names Proscar (5 mg/day finasteride) for BPH and Propecia (1 mg/day finasteride) for MPB. Of note, data from clinical trials has not demonstrated efficacy of a 5 mg dose of finasteride over a 1 mg dose in androgenic alopecia.

Chemical synthesis

Avodart (dutasteride) 500 µg soft capsules

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

See also

• Finasteride, related 5-alpha reductase inhibitor.

References

External links

• Avodart | Official website

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 前立腺癌における化学的予防策 chemoprevention strategies in prostate cancer
• 2. 男性における男性型脱毛症の治療 treatment of androgenetic alopecia in men
• 3. 前立腺肥大症の内科的治療 medical treatment of benign prostatic hyperplasia
• 4. 早期前立腺癌の男性に対する能動的サーベイランス active surveillance for men with early prostate cancer
• 5. 限局性前立腺癌治療後の血清PSAの上昇：全身療法 rising serum psa after treatment for localized prostate cancer systemic therapy

English Journal

• Re: Dutasteride Reduces Prostatitis Symptoms Compared With Placebo in Men Enrolled in the REDUCE Study.

• Schaeffer AJ.SourceDepartment of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Tarry 16-703, Chicago, IL 60611-3008, USA.
• European urology.Eur Urol.2012 Feb;61(2):425.
• PMID 22186347

• Efficacy and safety of dutasteride in chinese adults with symptomatic benign prostatic hyperplasia: a randomized, double-blind, parallel-group, placebo-controlled study with an open-label extension.

• Na Y, Ye Z, Zhang S.SourceDepartment of Urology, Beijing Shougang Hospital, Affiliated Hospital of Beijing University, Beijing, China.
• Clinical drug investigation.Clin Drug Investig.2012 Jan 1;32(1):29-39. doi: 10.2165/11593750-000000000-00000.
• Background: Dutasteride is a dual inhibitor of type I and type II 5α-reductases and provides nearly complete suppression of dihydrotestosterone, which plays a key role in the aetiology and development of benign prostatic hyperplasia (BPH). Most knowledge about the efficacy and safety of dutasteride
• PMID 22017520

Japanese Journal

• PP-897 TUR-P前に投与するDutasterideの効果(発表・討論,一般演題ポスター,第99回日本泌尿器科学会総会)

• 財津 將嘉,山ノ井 万里子,三上 耕治,竹島 雄太,岡本 直彦,今尾 貞夫,武内 巧
• 日本泌尿器科學會雜誌 102(2), 554, 2011-03-20
• NAID 110008613270

• PP-894 5α還元酵素阻害剤dutasterideの臨床成績と使用前後のステロイドホルモン動態変化の検証(発表・討論,一般演題ポスター,第99回日本泌尿器科学会総会)

• 前田 高宏,菊地 栄次,本間 桂子,長谷川 政徳,鈴木 賢次郎,篠田 和伸,香野 日高,水野 隆一,長田 治彦,浅沼 宏,宮嶋 哲,中川 健,大家 基嗣
• 日本泌尿器科學會雜誌 102(2), 554, 2011-03-20
• NAID 110008613267

Related Links

• アボダート（デュタステライド） 0.5 mg(Avodart (Dutasteride ...

※この商品に関係するニュース記事へのリンクがページ最下部にあります。 「有効成分」 デュタステライド／デュタステリド(Dutasteride) 「同一成分含有商品」 アボダート（デュタステライド） 0.5 mg (30カプセル) 5380 円

• Get dutasteride info - A DHT inhibitor also known as Avodart ...

Dutasteride.org is your source of infomation about a new dual 5 alpha-reductase inhibitor used for lowering DHT and treating BPH and hair loss. ... Dutasteride.org is an independent clearinghouse for information about ...

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リンク元	「デュタステリド」「AVODART」

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商

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関

その他のホルモン剤。前立腺肥大症

• テストステロン5α還元酵素阻害薬:前立腺肥大治療
• 用法：デュタステリドとして1回0.5mgを1日1回経口投与
• 禁忌：重度の肝機能障害

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　　[★] デュタステリド dutasteride