请输入您要查询的百科知识：

　

词条 Danazol
释义

  1. Medical uses

     Available forms 

  2. Contraindications

  3. Side effects

  4. Pharmacology

     Pharmacodynamics  Modulation of steroid hormone receptors  Inhibition of steroidogenesis enzymes  Occupation and downregulation of carrier proteins  Antigonadotropic activity  Mechanism of action in endometriosis  Effects in men  Pharmacokinetics 

  5. Chemistry

  6. History

  7. Society and culture

     Generic names  Brand names  Availability 

  8. Research

  9. References

  10. Further reading

{{Distinguish|Danabol}}{{Drugbox
| verifiedrevid = 464367029
| IUPAC_name = (1S,2R,13R,14S,17R,18S)-17-ethynyl-2,18-dimethyl-7-oxa-6-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4(8),5,9-trien-17-ol
| image = Danazol.svg
| width = 225px
| image2 = Danazol molecule ball.png
| width2 = 235px
| tradename = Danatrol, Danocrine, Danol, Danoval, others
| Drugs.com = {{drugs.com|monograph|danazol}}
| MedlinePlus = a682599
| pregnancy_AU = D
| pregnancy_US = X
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = By mouth
| class = Androgen; Anabolic steroid; Progestin; Progestogen; Antigonadotropin; Steroidogenesis inhibitor; Antiestrogen
| bioavailability = Saturable with dosage, higher with food intake[1]
| protein_bound = To albumin, {{abbrlink|SHBG|sex hormone-binding globulin}}, {{abbrlink|CBG|corticosteroid-binding globulin}}[1][3][4]
| metabolism = Liver (CYP3A4)[5][6]
| metabolites = • {{abbr|2-OHM-Ethisterone|2-Hydroxymethylethisterone}}[6]
• Ethisterone[8][9]
| elimination_half-life = Acute: 3–10 hours[5][1]
Chronic: 24–26 hours[5]
| excretion = Urine, feces[5][1]
| IUPHAR_ligand = 6942
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 17230-88-5
| ATC_prefix = G03
| ATC_suffix = XA01
| PubChem = 28417
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01406
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 26436
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = N29QWW3BUO
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00289
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4315
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1479
| synonyms = WIN-17757; 2,3-Isoxazolethisterone; 2,3-Isoxazol-17α-ethynyltestosterone; 17α-Ethynyl-17β-hydroxyandrost-4-en-[2,3-d]isoxazole
| C=22 | H=27 | N=1 | O=2
| molecular_weight = 337.463 g/mol
| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CC5=C(C[C@]34C)C=NO5
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H27NO2/c1-4-22(24)10-8-18-16-6-5-15-11-19-14(13-23-25-19)12-20(15,2)17(16)7-9-21(18,22)3/h1,11,13,16-18,24H,5-10,12H2,2-3H3/t16-,17+,18+,20+,21+,22+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = POZRVZJJTULAOH-LHZXLZLDSA-N
}}Danazol, sold under the brand name Danocrine among others, is a medication which is used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema, and other conditions.[2][3][4][5][6] It is taken by mouth.[3]

The use of danazol is limited by masculinizing side effects such as acne, excessive hair growth, and voice deepening.[3][7] Danazol has a complex mechanism of action, and is characterized as a weak androgen and anabolic steroid, a weak progestogen, a weak antigonadotropin, a weak steroidogenesis inhibitor, and a functional antiestrogen.[4][24][25][26]

Danazol was discovered in 1963 and was introduced for medical use in 1971.[24][28][29][30] Due to their improved side-effect profiles, particularly their lack of masculinizing side effects, danazol has largely been replaced by gonadotropin-releasing hormone analogues (GnRH analogues) in the treatment of endometriosis.[8]

{{TOC limit|3}}

Medical uses

Danazol is used primarily in the treatment of endometriosis. It has also been used – mostly off-label – for other indications, namely in the management of menorrhagia, fibrocystic breast disease, immune thrombocytopenic purpura, premenstrual syndrome, breast pain, and hereditary angioedema.[9] Although not currently a standard treatment for menorrhagia, danazol demonstrated significant relief in young women with menorrhagia in a study, and, because of a lack of a significant adverse effects, it was proposed as an alternative treatment.[10] Danazol appears to be useful in the treatment of systemic lupus erythematosus.[11]

Available forms

Danazol comes in the form of 50, 100, and 200 mg oral capsules.[3] It is taken at a dose of 50 to 400 mg two or three times per day, for a total of 100 to 800 mg per day depending on the indication.[3]

Contraindications

Danazol is contraindicated during pregnancy because it has the potential to virilize female fetuses. Women taking danazol should practice effective contraception to prevent pregnancy if sexually active.[37]

Since danazol is metabolized by the liver, it cannot be used by patients with liver disease, and in patients receiving long-term therapy, liver function must be monitored on a periodic basis.[12]

Side effects

{{See also|Anabolic steroid#Adverse effects}}

Androgenic side effects are of concern, as some women taking danazol may experience unwanted hair growth (hirsutism), acne, irreversible deepening of the voice,[8] or adverse blood lipid profiles.[37] In addition, breast atrophy and decreased breast size may occur.[8] The drug may also cause hot flashes, elevation of liver enzymes, and mood changes.[37] Some patients who use danazol experience weight gain and fluid retention. Due to its side effects, danazol is seldom prescribed continuously beyond six months.

The use of danazol for endometriosis has been linked to an increased risk of ovarian cancer.[13] Patients with endometriosis have specific risk factors for ovarian cancer, so this may not apply for other uses. Danazol, like most other anabolic steroids, has been linked with an increased risk of liver tumors. These are generally benign.[14]

Pharmacology

Pharmacodynamics

Danazol possesses a complex pharmacology, with multiple mechanisms of action.[15][24][16] These include direct binding to and activation of sex hormone receptors, direct inhibition of enzymes involved in steroidogenesis, and direct binding to and occupation of steroid hormone carrier proteins and consequent displacement of steroid hormones from these proteins.[8][15][24][16] The drug is characterized as a weak androgen and anabolic, a weak progestogen, a weak antigonadotropin, a weak steroidogenesis inhibitor, and a functional antiestrogen.[24][17]

Modulation of steroid hormone receptors

Danazol is described as a possessing high affinity for the androgen receptor (AR), moderate affinity for the progesterone receptor (PR) and glucocorticoid receptor (GR), and poor affinity for the estrogen receptor (ER).[8][15] As an androgen, danazol is described as weak, being about 200-fold less potent than testosterone in bioassays.[17] The drug can act as both an agonist and antagonist of the PR depending on the bioassay, indicating that it could be regarded as a selective progesterone receptor modulator (SPRM).[15] Although the affinity and efficacy of danazol itself at the PR are relatively low, ethisterone, one of the major metabolites of danazol, is described as a weak progestogen (and has been employed clinically as a progestogen), and this presumably serves to increase the in vivo progestogenic activity of danazol.[18] The activity of danazol at the ER is considered to be minimal, although at very high concentrations the drug can act significantly as an ER agonist.[15] Danazol is considered to act significantly as an agonist of the GR, and, thus, as a glucocorticoid.[15] In accordance, it can suppress the immune system at sufficient dosages.[15][24][17]

Relative affinities (%) of danazol and metabolites
Steroid PR|Progesterone receptorAR|Androgen receptorER|Estrogen receptorGR|Glucocorticoid receptorMR|Mineralocorticoid receptorSHBG|Sex hormone-binding globulinCBG|Corticosteroid binding globulin
Danazol 9 8 ? <0.2a ? 40 10
Ethisterone 35 <1 <1 <1b <1 92–121 0.33
5α-Dihydroethisterone 12 38–100c 4 120b ? 100 ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the {{abbrlink|PR|progesterone receptor}}, testosterone (c = {{abbr|DHT|dihydrotestosterone}}) for the {{abbrlink|AR|androgen receptor}}, cortisol for the {{abbrlink|GR|glucocorticoid receptor}} (b = dexamethasone), aldosterone for the {{abbrlink|MR|mineralocorticoid receptor}}, {{abbr|DHT|dihydrotestosterone}} for {{abbrlink|SHBG|sex hormone-binding globulin}}, and cortisol for {{abbrlink|CBG|corticosteroid-binding globulin}}. a = 1-hour incubation time (4 hours is standard for this assay; may affect affinity value). Sources: [19][20][21][22][23][24]
Absolute affinities (nM) of danazol
Receptor Affinity Action
Androgen receptor 90 Agonist
Progesterone receptor 6,000 Agonist–antagonist
Glucocorticoid receptor 5,000 Agonist
Estrogen receptor 80,000 Agonist
Sources: [8][15]

Inhibition of steroidogenesis enzymes

Danazol has been found to act as an inhibitor, to varying extents, of a variety of steroidogenic enzymes, including cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase, 17α-hydroxylase, 17,20-lyase, 17β-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11β-hydroxylase.[15] It has also been found to be a weak inhibitor of steroid sulfatase (Ki = 2.3–8.2 μM), the enzyme that converts {{abbrlink|DHEA-S|dehydroepiandrosterone sulfate}} into {{abbrlink|DHEA|dehydroepiandrosterone}} and estrone sulfate into estrone (which can then respectively be transformed into estrone (with androstenedione as an intermediate) and estradiol),[25] though another study reported its inhibition to be potent and potentially clinically relevant.[26] Although in contradiction with the above data, another study found that danazol weakly inhibited aromatase as well, with 44% inhibition at a concentration of 10 μM.[25]

In accordance with its steroidogenesis inhibition, clinical studies have demonstrated that danazol directly and markedly inhibits adrenal, ovarian, and testicular steroidogenesis in vivo.[15] The enzymatic production of estradiol, progesterone, and testosterone have all specifically been found to be inhibited.[15]

Danazol at steroiodgenic enzymes
Enzyme Affinity (Ki) Inhibition type Estimated inhibition at 2 μM
Cholesterol side-chain cleavage enzyme 20 μM Competitive ?
3β-Hydroxysteroid dehydrogenase/Δ5-4 isomerase 5.8 μM Competitive 4.3%
17α-Hydroxylase 2.4 μM Competitive 2.9%
17,20-Lyase 1.9 μM Competitive 3.9%
17β-Hydroxysteroid dehydrogenase 4.4 μM Competitive 15%
21-Hydroxylase 0.8 μM Competitive 37%
11β-Hydroxylase 1 μM Competitive 21%
Aromatase >100 μM – 0%
Sources: [15]

For reference, circulating concentrations of danazol are in the range of 2 μM at a dosage of 600 mg/day in women.[15]

Occupation and downregulation of carrier proteins

Protein binding of testosterone in women
Group Free Albumin SHBG
Normal (no danazol) 1% 39% 60%
Danazol treatment 3% 79% 18%
Sources: [15]

Danazol is known to bind to two steroid hormone carrier proteins: sex hormone-binding globulin (SHBG), which binds androgens and estrogens; and corticosteroid-binding globulin (CBG), which binds progesterone and cortisol.[8][15] Binding of danazol to SHBG is considered to be more important clinically.[15] By occupying SHBG and CBG, danazol increases the ratio of free to plasma protein-bound testosterone, estradiol, progesterone, and cortisol.[8][15] The table to the right shows the difference in testosterone levels in premenopausal women treated with danazol.[15]

As can be seen, the percentage of free testosterone is tripled in women being treated with danazol.[15][27] The ability of danazol to increase free testosterone levels suggests that a portion of its weak androgenic effects are mediated indirectly by facilitating the activity of testosterone and dihydrotestosterone through the displacement of them from SHBG.[15][27] In addition to binding to and occupying SHBG however, danazol also decreases the hepatic production of SHBG and therefore SHBG levels, and so downregulation of SHBG may be involved as well.[8][15] Danazol likely decreases hepatic production of SHBG by reducing estrogenic and increasing androgenic activity in the liver (as androgens and estrogens decrease and increase, respectively, hepatic SHBG synthesis).[28] In accordance with the notion that suppression of SHBG is involved in the androgenic effects of danazol, the drug has synergistic rather than additive androgenic effects in combination with testosterone in bioassays (which is most likely secondary to the increased free testosterone levels).[17]

It is noteworthy that 2-hydroxymethylethisterone, a major metabolite of danazol, circulates at concentrations 5–10 times greater than those of danazol and is twice as potent as danazol in displacing testosterone from SHBG.[29] As such, most of the occupation of SHBG by danazol may actually be due to this metabolite.[29]

Antigonadotropic activity

Via its weak progestogenic and androgenic activity, through activation of the PR and AR in the pituitary gland, danazol produces antigonadotropic effects.[15] Although its does not significantly affect basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in premenopausal women (and hence does not profoundly suppress gonadotropin or sex hormone levels like other, stronger antigonadotropins do),[30] the drug prevents the mid-cycle surge in the levels of these hormones during the menstrual cycle.[8][17][31][32][33] By doing this, it suppresses increases in estrogen and progesterone levels at this time and prevents ovulation.[17][31][32][33]

Mechanism of action in endometriosis

Because danazol reduces estrogen production and levels,[30] it has functional antiestrogenic properties.[34] The combination of its antiestrogenic, androgenic, and progestogenic or antiprogestogenic actions cause atrophy of the endometrium, which alleviates the symptoms of endometriosis.[8][15][17][30][35]

Effects in men

In men, danazol has been found to inhibit gonadotropin secretion and markedly decrease testosterone levels, likely due to its actions as a steroidogenesis inhibitor and antigonadotropin.[115] However, even at the highest dosage assessed (800 mg/day), spermatogenesis remained unaffected.[115]

Pharmacokinetics

The bioavailability of danazol is low.[8] In addition, circulating levels of danazol do not increase proportionally with increasing doses, indicating that there is a saturation of bioavailability.[3] With single-dose administration, it has been found that a 4-fold increase in dosage of danazol increased peak levels only by 1.3- and 2.2-fold and area-under-the-curve levels by 1.6- and 2.5-fold in the fasted and fed states, respectively.[3] Similar findings were observed for chronic administration.[3] Intake of danazol with food (>30 grams of fat) has been found to increase the bioavailability and peak levels of danazol by 3- to 4-fold with a single dose and by 2- to 2.5-fold with chronic administration.[3] Following administration of danazol, peak concentrations occur after 2 to 8 hours, with a median of 4 hours.[3] Steady-state levels of danazol are achieved after 6 days of twice-daily administration.[3] Danazol is lipophilic and can partition into cell membranes, which indicates that it is likely to distribute deeply into tissue compartments.[3] The volume of distribution of danazol is 3.4 L.[8] Danazol is known to be plasma protein bound to albumin, SHBG, and CBG.[1][8][15]

Danazol is metabolized in the liver by enzymes such as CYP3A4.[2][6] Its elimination half-life has varied across studies, but has been found to be 3 to 10 hours after a single dose and 24 to 26 hours with repeated administration.[2][3] The major metabolites of danazol are 2-hydroxymethylethisterone (also known as 2-hydroxymethyldanazol; formed by CYP3A4 and described as inactive) and ethisterone (a progestogen and androgen),[6][3][36][37] and other, minor metabolites include δ2-hydroxymethylethisterone, 6β-hydroxy-2-hydroxymethylethisterone, and δ1-6β-hydroxy-2-hydroxymethylethisterone.[38] At least 10 different metabolites have been identified.[3] Danazol is eliminated in urine and feces, with the two primary metabolites in urine being 2-hydroxymethylethisterone and ethisterone.[3]

Chemistry

{{See also|List of androgens/anabolic steroids|List of progestogens}}

Danazol, also known as 2,3-isoxazol-17α-ethynyltestosterone or as 17α-ethynyl-17β-hydroxyandrost-4-en-[2,3-d]isoxazole, is a synthetic androstane steroid and a derivative of testosterone and ethisterone (17α-ethynyltestosterone).[4][5][39] It is specifically the derivative of ethisterone where the C3 ketone is replaced with a 2,3-isoxazole moiety (i.e., an isoxazole ring is fused to the A ring at the C2 and C3 positions).[40][41] Ethisterone is a weak progestin with weak androgenic activity.[42]

History

Danazol was synthesized in 1963 by a team of scientists at Sterling Winthrop in Rensselaer, New York by a team that included Helmutt Neumann, Gordon Potts, W.T. Ryan, and Frederik W. Stonner.[43][44] It was approved by the {{abbrlink|U.S.|United States}} Food and Drug Administration in 1971 as the first drug in the country to specifically treat endometriosis.[41][45]

Society and culture

Generic names

Danazol is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, {{abbrlink|DCIT|Denominazione Comune Italiana}}, and {{abbrlink|JAN|Japanese Accepted Name}}.[2][4][5][6][154] It is also known by its developmental code name WIN-17757.[2][4][5][6][154]

Brand names

Danazol is or has been marketed under many brand names throughout the world including Anargil, Azol, Benzol, Bonzol, Cyclolady, Cyclomen, Danal, Danalol, Danamet, Danamin, Danasin, Danatrol, Danazant, Danazol, Danocrine, Danodiol, Danogen, Danokrin, Danol, Danonice, Danoval, Danzol, Dogalact (veterinary), Dorink, Dzol, Ectopal, Elle, Gonablok, Gong Fu Yi Kang, Gynadom, Kodazol, Kupdina, Ladogal, Lozana, Mastodanatrol, Nazol, Norciden, Vabon, and Winobanin.[2][4][5][6][46]

Availability

Danazol is available in the United States, Europe, and widely elsewhere throughout the world.[2][5][46]

Research

Low-dose danazol has been investigated in the treatment of diabetic macular edema in a phase III clinical trial.[47][48]

A 2016 phase I/II prospective study orally administered 800 mg per day to 27 patients with telomere diseases. The primary efficacy endpoint was a 20% reduction in the annual rate of telomere attrition measured. Toxic effects formed the primary safety endpoint. The study was halted early, after telomere attrition was reduced in all 12 patients who could be evaluated. 12 of 27 patients achieved the primary efficacy end point, 11 of whom increased telomere length at 24 months. Hematologic responses (secondary efficacy endpoint) occurred in 10 of 12 patients who could be evaluated at 24 months. Elevated liver-enzyme levels and muscle cramps (known adverse effects) of grade 2 or less occurred in 41% and 33% of the patients, respectively.[49]

References

1. ^1 {{cite book|author1=J.P. Griffin|author2=P.F. D'Arcy|title=A Manual of Adverse Drug Interactions|url=https://books.google.com/books?id=rmx2fLEdZvwC&pg=PA194|date=17 November 1997|publisher=Elsevier|isbn=978-0-08-052583-9|pages=194–}}
2. ^1 2 3 4 5 6 7 8 9 10 {{cite web|title=Danazol|work=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|date=30 October 2013|accessdate=1 April 2014|url=http://www.medicinescomplete.com/mc/martindale/current/9035-v.htm|editor=Brayfield, A}}
3. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017557s033s039s040s041s042lbl.pdf
4. ^1 2 3 4 {{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA345|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=345–}}
5. ^1 2 3 4 5 {{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA293|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=293–}}
6. ^1 2 3 {{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA91|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=91–}}
7. ^{{cite journal |author=Selak V, Farquhar C, Prentice A, Singla A |title=Danazol for pelvic pain associated with endometriosis |journal=Cochrane Database of Systematic Reviews |volume= |issue=4 |pages=CD000068 |year=2007 |pmid=17943735 |doi=10.1002/14651858.CD000068.pub2 |editor1-last=Farquhar |editor1-first=Cindy}}
8. ^1 2 3 4 5 6 7 8 9 10 11 12 {{cite book|author1=Eberhard Nieschlag|author2=Hermann M. Behre|author3=Susan Nieschlag|title=Andrology: Male Reproductive Health and Dysfunction|url=https://books.google.com/books?id=mEgckDNkonUC&pg=PA426|date=13 January 2010|publisher=Springer Science & Business Media|isbn=978-3-540-78355-8|pages=426–428}}
9. ^{{cite book |author1=Rod Flower |author2=Humphrey P. Rang |author3=Maureen M. Dale |author4=Ritter, James M. |title=Rang & Dale's pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2007 |pages= |isbn=0-443-06911-5 |oclc= |doi= |accessdate=}}
10. ^{{cite journal | year = | title = Efficacy of vaginal danazol treatment in women with menorrhagia during fertile age | url = | journal = Fertil. Steril.| volume = 92| issue = 4| pages = 1351–4| doi = 10.1016/j.fertnstert.2008.08.017 | pmid = 18930222 | date=October 2009 | last1 = Luisi | first1 = S | last2 = Razzi | first2 = S | last3 = Lazzeri | first3 = L | last4 = Bocchi | first4 = C | last5 = Severi | first5 = FM | last6 = Petraglia | first6 = F}}
11. ^{{cite journal | vauthors = Letchumanan P, Thumboo J | title = Danazol in the treatment of systemic lupus erythematosus: a qualitative systematic review | journal = Semin. Arthritis Rheum. | volume = 40 | issue = 4 | pages = 298–306 | date = February 2011 | pmid = 20541792 | doi = 10.1016/j.semarthrit.2010.03.005 | url = }}
12. ^{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682599.html|title=Danazol: MedlinePlus Drug Information|website=medlineplus.gov|language=en|access-date=2018-11-07}}
13. ^{{cite journal |vauthors=Cottreau CM, Ness RB, Modugno F, Allen GO, Goodman MT |title=Endometriosis and Its Treatment with Danazol or Lupron in Relation to Ovarian Cancer |journal=Clinical Cancer Research |volume=9 |issue= 14|pages=5142–4 |year=2003 |pmid=14613992 |doi=}}
14. ^{{cite journal |vauthors=Velazquez I, Alter BP |title=Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions |journal=Am. J. Hematol. |volume=77 |issue=3 |pages=257–67 |year=2004 |pmid=15495253 |doi=10.1002/ajh.20183}}
15. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 {{cite book|author1=Eric J. Thomas|author2=John Rock|title=Modern Approaches to Endometriosis|url=https://books.google.com/books?id=AFP1CAAAQBAJ&pg=PA241|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-3864-2|pages=239–256}}
16. ^1 2 {{cite book|author=Aurel Lupulescu|title=Hormones and Vitamins in Cancer Treatment|url=https://books.google.com/books?id=VddUa-2cp-YC&pg=PA103|date=24 October 1990|publisher=CRC Press|isbn=978-0-8493-5973-6|pages=103–}}
17. ^1 2 3 4 5 6 7 {{cite book|author1=Albert Altchek|author2=Liane Deligdisch|author3=Nathan Kase|title=Diagnosis and Management of Ovarian Disorders|url=https://books.google.com/books?id=vds_TQpTIhoC&pg=PA376|date=4 September 2003|publisher=Academic Press|isbn=978-0-08-049451-7|pages=376–}}
18. ^1 {{cite book|author=Robert J. Kurman|title=Blaustein's Pathology of the Female Genital Tract|url=https://books.google.com/books?id=sM3eBwAAQBAJ&pg=PA390|date=17 April 2013|publisher=Springer Science & Business Media|isbn=978-1-4757-3889-6|pages=390–}}
19. ^{{cite journal | vauthors = Ojasoo T, Raynaud JP, Doé JC | title = Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data | journal = J. Steroid Biochem. Mol. Biol. | volume = 48 | issue = 1 | pages = 31–46 | date = January 1994 | pmid = 8136304 | doi = 10.1016/0960-0760(94)90248-8 | url = }}
20. ^{{cite journal | vauthors = Ojasoo T, Raynaud JP | title = Unique steroid congeners for receptor studies | journal = Cancer Res. | volume = 38 | issue = 11 Pt 2 | pages = 4186–98 | date = November 1978 | pmid = 359134 | doi = | url = http://cancerres.aacrjournals.org/content/38/11_Part_2/4186.short}}
21. ^{{cite journal | vauthors = Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP | title = Steroid flexibility and receptor specificity | journal = J. Steroid Biochem. | volume = 13 | issue = 1 | pages = 45–59 | date = January 1980 | pmid = 7382482 | doi = 10.1016/0022-4731(80)90112-0 | url = }}
22. ^{{cite journal | vauthors = Pugeat MM, Dunn JF, Nisula BC | title = Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = J. Clin. Endocrinol. Metab. | volume = 53 | issue = 1 | pages = 69–75 | date = July 1981 | pmid = 7195405 | doi = 10.1210/jcem-53-1-69 | url = }}
23. ^{{cite journal | vauthors = Cunningham GR, Tindall DJ, Lobl TJ, Campbell JA, Means AR | title = Steroid structural requirements for high affinity binding to human sex steroid binding protein (SBP) | journal = Steroids | volume = 38 | issue = 3 | pages = 243–62 | date = September 1981 | pmid = 7197818 | doi = 10.1016/0039-128X(81)90061-1 | url = }}
24. ^{{cite journal | vauthors = Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J | title = 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism | journal = Invest New Drugs | volume = 30 | issue = 1 | pages = 59–78 | date = February 2012 | pmid = 20814732 | doi = 10.1007/s10637-010-9517-0 | url = }}
25. ^1 {{cite journal|last1=Shields-Botella|first1=J.|last2=Chetrite|first2=G.|last3=Meschi|first3=S.|last4=Pasqualini|first4=J.R.|title=Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells|journal=The Journal of Steroid Biochemistry and Molecular Biology|volume=93|issue=1|year=2005|pages=1–13|issn=0960-0760|doi=10.1016/j.jsbmb.2004.11.004|pmid=15748827}}
26. ^{{cite journal | vauthors = Carlström K, Döberl A, Pousette A, Rannevik G, Wilking N | title = Inhibition of steroid sulfatase activity by danazol | journal = Acta Obstet Gynecol Scand Suppl | volume = 123 | issue = | pages = 107–11 | year = 1984 | pmid = 6238495 | doi = | url = }}
27. ^1 {{cite book|author1=Richard A. Helms|author2=David J. Quan|title=Textbook of Therapeutics: Drug and Disease Management|url=https://books.google.com/books?id=aVmRWrknaWgC&pg=PA383|year=2006|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-5734-8|pages=383–}}
28. ^{{cite book|author1=Sarah H. Wakelin|author2=Howard I. Maibach|author3=Clive B. Archer|title=Handbook of Systemic Drug Treatment in Dermatology, Second Edition|url=https://books.google.com/books?id=fCysCQAAQBAJ&pg=PA23|date=21 May 2015|publisher=CRC Press|isbn=978-1-4822-2286-9|pages=23–}}
29. ^1 {{cite book|author=Ulrich Westphal|title=Steroid-Protein Interactions II|url=https://books.google.com/books?id=3DD6CAAAQBAJ&pg=PA256|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-82486-9|pages=256–}}
30. ^1 2 {{cite book|author1=C. David Tollison|author2=John R. Satterthwaite|author3=Joseph W. Tollison|title=Practical Pain Management|url=https://books.google.com/books?id=BbmI8FCssdEC&pg=PA479|date=January 2002|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-3160-7|pages=479–}}
31. ^1 2 3 4 {{cite book|last=Hoffman|first=Barbara L|author2=Schorge JO |author3=Schaffer JI |author4=Halvorson LM |author5=Bradshaw KD |author6=Cunningham FG |author7=Calver LE |title=Williams Gynecology: Chapter 10, Endometriosis|publisher=McGraw-Hill Medical|location=New York|isbn=9780071716727|url=http://www.accessmedicine.com/content.aspx?aID=56699002.|edition=2nd}}
32. ^1 {{cite journal|last=Floyd|first=WS|title=Danazol: endocrine and endometrial effects.|journal=Int J Fertil.|year=1980|pages=75–80|pmid=6104649|volume=25|issue=1}}
33. ^1 {{cite book|last1=Katzung|first1=Bertram|title=Basic & Clinical Pharmacology|date=2012|publisher=McGraw Hill|isbn=978-0-07-176401-8|page=732|edition=12}}
34. ^{{cite book|author=Robert B. Taylor|title=Taylor’s Family Medicine Review|url=https://books.google.com/books?id=udkhAQAAMAAJ|date=25 September 1998|publisher=Springer New York|isbn=978-0-387-98569-5|page=221}}
35. ^{{cite journal|last=Fedele|first=L|author2=Marchini, M |author3=Bianchi, S |author4=Baglioni, A |author5=Bocciolone, L |author6= Nava, S |title=Endometrial patterns during danazol and buserelin therapy for endometriosis: comparative structural and ultrastructural study.|journal=Obstetrics and gynecology|date=July 1990|volume=76|issue=1|pages=79–84|pmid=2113661}}
36. ^1 2 3 {{cite book|author=Florencio Zaragoza Dörwald|title=Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds|url=https://books.google.com/books?id=YTeY9ZEfNccC&pg=PA485|date=4 February 2013|publisher=John Wiley & Sons|isbn=978-3-527-64565-7|pages=485–}}
37. ^{{cite book|author1=Ashraf Mozayani|author2=Lionel Raymon|title=Handbook of Drug Interactions: A Clinical and Forensic Guide|url=https://books.google.com/books?id=NhBJ6kg_uP0C&pg=PA646|date=18 September 2011|publisher=Springer Science & Business Media|isbn=978-1-61779-222-9|pages=646–}}
38. ^https://gp2u.com.au/static/pdf/A/AZOL-PI.pdf
39. ^1 2 {{cite journal | vauthors = Bruneteau DW, Bernard I, Greenblatt RB | title = [Clinical studies with a new antigonadotropin: Danazol] | language = French | journal = Gynecologie | volume = 25 | issue = 1 | pages = 41–5 | date = 1974 | pmid = 4422449 | doi = | url = https://www.popline.org/node/503222 | quote = Danazol (2-3-isoxazol-17alpha-ethinyl-testosterone)}}
40. ^1 2 3 4 {{cite book|author1=Thomas L. Lemke|author2=David A. Williams|title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1361|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=1361–}}
41. ^1 2 3 4 5 6 7 {{cite book|author1=Howard W. Jones|author2=John A. Rock|title=Te Linde's Operative Gynecology|url=https://books.google.com/books?id=iK4kCgAAQBAJ&pg=PT1327|date=10 July 2015|publisher=Wolters Kluwer Health|isbn=978-1-4963-1521-2|pages=1327–1330}}
42. ^{{cite book|author=Dr. S. S. Kadam|title=PRINCIPLES OF MEDICINAL CHEMISTRY Vol. - II|url=https://books.google.com/books?id=Z7Pb3lJuRksC&pg=PA364|date=July 2007|publisher=Pragati Books Pvt. Ltd.|isbn=978-81-85790-03-9|pages=364–}}
43. ^1 G.P. Ellis and G.B. Ellis, {{Doi|10.1016/S0079-6468(08)70187-5}} (1979), pp. 126, note 158, 130, notes 1513, 2369, citing {{Doi|10.1021/jm00299a034}}
44. ^1 {{cite book|author1=Alan N. Elias|author2=Grant Gwinup|title=Hirsutism|url=https://books.google.com/books?id=4OJsAAAAMAAJ|date=1 January 1983|publisher=Praeger|page=70}}
45. ^1 {{cite journal |vauthors=Dmowski WP, Scholer HF, Mahesh VB, Greenblatt RB |title=Danazol--a synthetic steroid derivative with interesting physiologic properties |journal=Fertil. Steril. |volume=22 |issue=1 |pages=9–18 |year=1971 |pmid=5538758 |doi=}}
46. ^1 2 3 https://www.drugs.com/international/danazol.html
47. ^{{cite web|title=A Safety and Efficacy Study of Oral Danazol (a Previously Approved Drug)in the Treatment of Diabetic Macular Edema|url=https://clinicaltrials.gov/ct2/show/NCT01821677|website=Clinicaltrials.gov|publisher=Ampio Pharmaceuticals. Inc.|accessdate=27 June 2015}}
48. ^{{cite news|title=Ampio Pharmaceuticals Announces Additional Statistically Significant Study Results for Optina™ in the Treatment of Diabetic Macular Edema (DME)|url=http://ampiopharma.com/news/ampio-pharmaceuticals-announces-additional-statistically-significant-study-results-for-optina-in-the-treatment-of-diabetic-macular-edema-dme/|accessdate=27 June 2015|publisher=Ampio Pharmaceuticals. Inc.}}
49. ^{{cite journal | vauthors = Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, Hardy N, Mihalek AD, Lingala S, Kim YJ, Yao J, Jones E, Gochuico BR, Heller T, Wu CO, Calado RT, Scheinberg P, Young NS | title = Danazol Treatment for Telomere Diseases | journal = N. Engl. J. Med. | volume = 374 | issue = 20 | pages = 1922–31 | date = May 2016 | pmid = 27192671 | pmc = 4968696 | doi = 10.1056/NEJMoa1515319 | url = }}

Further reading

  • {{cite journal | vauthors = Dmowski WP | title = Endocrine properties and clinical application of danazol | journal = Fertil. Steril. | volume = 31 | issue = 3 | pages = 237–51 | date = March 1979 | pmid = 374128 | doi = | url = }}
  • {{cite journal | vauthors = Fraser IS | title = Danazol--a steroid with a unique combination of actions | journal = Scott Med J | volume = 24 | issue = 2 | pages = 147–50 | date = April 1979 | pmid = 386503 | doi = 10.1177/003693307902400209 | url = }}
  • {{cite journal | vauthors = Potts GO, Schane HP, Edelson J | title = Pharmacology and pharmacokinetics of danazol | journal = Drugs | volume = 19 | issue = 5 | pages = 321–30 | date = May 1980 | pmid = 6993179 | doi = 10.2165/00003495-198019050-00001 | url = }}
  • {{cite journal | vauthors = Jenkin G | title = Review: The mechanism of action of danazol, a novel steroid derivative | journal = Aust N Z J Obstet Gynaecol | volume = 20 | issue = 2 | pages = 113–8 | date = May 1980 | pmid = 6998453 | doi = 10.1111/j.1479-828X.1980.tb00107.x | url = }}
  • {{cite journal | vauthors = Barbieri RL, Ryan KJ | title = Danazol: endocrine pharmacology and therapeutic applications | journal = Am. J. Obstet. Gynecol. | volume = 141 | issue = 4 | pages = 453–63 | date = October 1981 | pmid = 7025640 | doi = 10.1016/0002-9378(81)90611-6 | url = }}
  • {{cite journal | vauthors = Dmowski WP | title = Danazol. A synthetic steroid with diverse biologic effects | journal = J Reprod Med | volume = 35 | issue = 1 Suppl | pages = 69–74; discussion 74–5 | date = January 1990 | pmid = 2404115 | doi = | url = }}
  • {{cite journal | vauthors = Barbieri RL | title = Danazol: molecular, endocrine, and clinical pharmacology | journal = Prog. Clin. Biol. Res. | volume = 323 | issue = | pages = 241–52 | date = 1990 | pmid = 2406750 | doi = | url = }}
  • {{cite journal | vauthors = Hughes E, Brown J, Tiffin G, Vandekerckhove P | title = Danazol for unexplained subfertility | journal = Cochrane Database Syst Rev | volume = | issue = 1 | pages = CD000069 | date = January 2007 | pmid = 17253444 | doi = 10.1002/14651858.CD000069.pub2 | url = }}
  • {{cite journal | vauthors = Beaumont H, Augood C, Duckitt K, Lethaby A | title = Danazol for heavy menstrual bleeding | journal = Cochrane Database Syst Rev | volume = | issue = 3 | pages = CD001017 | date = July 2007 | pmid = 17636649 | doi = 10.1002/14651858.CD001017.pub2 | url = }}
  • {{cite journal | vauthors = Selak V, Farquhar C, Prentice A, Singla A | title = Danazol for pelvic pain associated with endometriosis | journal = Cochrane Database Syst Rev | volume = | issue = 4 | pages = CD000068 | date = October 2007 | pmid = 17943735 | doi = 10.1002/14651858.CD000068.pub2 | url = }}
  • {{cite journal | vauthors = Craig TJ | title = Appraisal of danazol prophylaxis for hereditary angioedema | journal = Allergy Asthma Proc | volume = 29 | issue = 3 | pages = 225–31 | date = 2008 | pmid = 18387221 | doi = 10.2500/aap.2008.29.3107 | url = }}
  • {{cite journal | vauthors = Ke LQ, Yang K, Li J, Li CM | title = Danazol for uterine fibroids | journal = Cochrane Database Syst Rev | volume = | issue = 3 | pages = CD007692 | date = July 2009 | pmid = 19588442 | doi = 10.1002/14651858.CD007692.pub2 | url = }}
  • {{cite journal | vauthors = Letchumanan P, Thumboo J | title = Danazol in the treatment of systemic lupus erythematosus: a qualitative systematic review | journal = Semin. Arthritis Rheum. | volume = 40 | issue = 4 | pages = 298–306 | date = February 2011 | pmid = 20541792 | doi = 10.1016/j.semarthrit.2010.03.005 | url = }}
{{Androgens and antiandrogens}}{{Progestogens and antiprogestogens}}{{Navboxes
| title = Pharmacodynamics
| titlestyle = background:#ccccff
| list1 ={{Androgen receptor modulators}}{{Estrogen receptor modulators}}{{Glucocorticoid receptor modulators}}{{Progesterone receptor modulators}}
}}

20 : 3β-Hydroxysteroid dehydrogenase inhibitors|11β-Hydroxylase inhibitors|17β-Hydroxysteroid dehydrogenase inhibitors|21-Hydroxylase inhibitors|Alcohols|Alkynes|Androgens and anabolic steroids|Androstanes|Antiestrogens|Antigonadotropins|Cholesterol side-chain cleavage enzyme inhibitors|CYP17A1 inhibitors|Glucocorticoids|Hepatotoxins|Isoxazoles|Progestogens|Steroid sulfatase inhibitors|Teratogens|Veterinary drugs|World Anti-Doping Agency prohibited substances
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/27 8:19:15