Abiraterone acetate






































































































































Abiraterone acetate
Abiraterone acetate.svg
Clinical data
Trade names Zytiga, Yonsa, others
Synonyms CB-7630; JNJ-212082; 17-(3-Pyridinyl)androsta-5,16-dien-3β-ol acetate

AHFS/Drugs.com
 Monograph
MedlinePlus a611046
License data



  • EU EMA: by INN


  • US FDA: abiraterone
Pregnancy
category



  • AU: D


  • US: X (Contraindicated)



Routes of
administration
By mouth (tablets)[1]
ATC code

  • L02BX03 (WHO)
Legal status
Legal status



  • AU: S4 (Prescription only)


  • CA: ℞-only


  • UK: POM (Prescription only)


  • US: ℞-only




Pharmacokinetic data
Bioavailability Unknown, but may be 50% at most on empty stomach[3]
Protein binding Abiraterone: ~99.8% (to albumin and α1-AGp)[3][1][2]
Metabolism
Esterases, CYP3A4, SULT2A1[2]
Metabolites
Abiraterone, others[1][3]
Elimination half-life
 Abiraterone: 12–24 hours[1][3]
Excretion
Feces: 88%[1][2]
Urine: 5%[1][2]
Identifiers
CAS Number

  • 154229-18-2 ☑Y
    154229-19-3 (abiraterone)

PubChem CID
  • 9821849
IUPHAR/BPS
  • 6745
DrugBank

  • DB05812 ☑Y
ChemSpider

  • 7997598 ☑Y
UNII
  • EM5OCB9YJ6
KEGG
  • D09701
ChEBI
  • CHEBI:68639
ChEMBL

  • ChEMBL271227 ☑Y
ECHA InfoCard
100.149.063 Edit this at Wikidata
Chemical and physical data
Formula
C26H33NO2
Molar mass 391.555 g/mol g·mol−1
3D model (JSmol)
  • Interactive image
Melting point 144 to 145 °C (291 to 293 °F) [4]

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  (verify)

Abiraterone acetate, sold under the brand name Zytiga among others, is an antiandrogen medication which is used in the treatment of prostate cancer.[1] It is specifically indicated for use in conjunction with castration and prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) and in the treatment of metastatic high-risk castration-sensitive prostate cancer (mCSPC).[1] It is taken by mouth once per day on an empty stomach.[1] Another brand name for it is Yonsa.[5]


Side effects of abiraterone acetate include fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flashes, diarrhea, vomiting, cough, headache, glucocorticoid deficiency, mineralocorticoid excess, and hepatotoxicity among others.[1] The drug is an androgen synthesis inhibitor – specifically, a CYP17A1 inhibitor – and thereby inhibits the production of androgens like testosterone and dihydrotestosterone in the body.[1] In doing so, it prevents the effects of these hormones in the prostate gland and elsewhere in the body.[1] Abiraterone acetate is a prodrug of abiraterone.[1]


Abiraterone acetate was first described in 1993 and was introduced for medical use in 2011.[6][7][8] It was approved for the treatment of mCRPC in 2011 and was subsequently approved for the treatment of mCSPC in 2018.[9] The medication is marketed widely throughout the world.[10] It is not available as a generic medication.[11]


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Contents






  • 1 Medical uses


    • 1.1 Prostate cancer


      • 1.1.1 Clinical effectiveness




    • 1.2 Available forms




  • 2 Contraindications


  • 3 Side effects


  • 4 Overdose


  • 5 Interactions


  • 6 Pharmacology


    • 6.1 Pharmacodynamics


      • 6.1.1 Antiandrogenic activity


      • 6.1.2 Estrogenic activity


      • 6.1.3 Other activities




    • 6.2 Pharmacokinetics




  • 7 Chemistry


  • 8 History


  • 9 Society and culture


    • 9.1 Generic names


    • 9.2 Brand names


    • 9.3 Availability




  • 10 Research


  • 11 See also


  • 12 References


  • 13 External links





Medical uses



Prostate cancer


Abiraterone acetate is indicated for use in combination with prednisone, a corticosteroid, as a treatment for mCRPC (previously called hormone-resistant or hormone-refractory prostate cancer).[12][13][14][15] This is a form of prostate cancer that is not responding to first-line androgen deprivation therapy or treatment with androgen receptor antagonists. Abiraterone acetate has received FDA (28 April 2011), EMA (23 September 2011), MHRA (5 September 2011) and TGA (1 March 2012) approval for this indication.[12][13][14][15] In Australia it is covered by the Pharmaceutical Benefits Scheme when being used to treat castration-resistant prostate cancer and given in combination with prednisone/prednisolone (subject to the conditions that the patient is not currently receiving chemotherapy, is either resistant or intolerant of docetaxel, has a WHO performance status of <2, and his disease has not since become progressive since treatment with PBS-subsidised abiraterone acetate has commenced).[16]


Abiraterone may be useful for prevention of the testosterone flare at the initiation of GnRH agonist therapy in men with prostate cancer.[17]



Clinical effectiveness


A phase III study in subjects previously treated with docetaxel started in 2008.[18] In September 2010, an independent panel found that the interim results in patients previously treated with docetaxel were so much better compared to those treated with placebo that it was unethical to keep half the study participants on placebo, and all patients began receiving the drug. Overall survival was increased by 3.9 months in to this study (14.8 months versus 10.9 months for placebo).[19]


A placebo-controlled double-blind randomized phase III study in patients with castration-refractory prostate cancer but who had not received chemotherapy opened to accrual in April 2009.[20][21] 1,088 men received either abiraterone acetate (1000 mg daily) plus prednisone (5 mg twice daily), or placebo plus prednisone. The median radiographic progression-free survival was 16.5 months with abiraterone acetate–prednisone and 8.3 months with prednisone alone (hazard ratio (HR) = 0.53; 95% confidence interval (CI), 0.45 to 0.62; P<0.001). After a median follow-up period of 22.2 months, overall survival was better with abiraterone acetate plus prednisone (median not reached) compared to placebo plus prednisone (27.2 months); HR = 0.75; 95% CI, 0.61 to 0.93; P=0.01).[22]



Available forms


Abiraterone acetate is available in the form of 250 mg and 500 mg film-coated oral tablets and 250 mg uncoated oral tablets.[1] It is used at a dosage of 1,000 mg orally once per day an empty stomach, in conjunction with castration (via GnRH analogue therapy or orchiectomy) and in combination with 5 mg prednisone orally twice per day.[1]



Contraindications


Contraindications include hypersensitivity to abiraterone acetate. Although documents state that it should not be taken by women who are or who may become pregnant,[13][23] there is no medical reason that any woman should take it. Women who are pregnant should not even touch the pills unless they are wearing gloves.[23] Other cautions include severe baseline hepatic impairment, mineralocorticoid excess, cardiovascular disease including heart failure and hypertension, uncorrected hypokalemia, and adrenocorticoid insufficiency.[24]



Side effects


Side effects by frequency:[12][13][14][15][24]


Very common (>10% frequency):




  • Urinary tract infection

  • Hypokalemia

  • Hypertension

  • Diarrhea

  • Peripheral edema



Common (1-10% frequency):




  • Hypertriglyceridaemia

  • Sepsis

  • Cardiac failure

  • Angina pectoris

  • Arrhythmia

  • Atrial fibrillation

  • Tachycardia


  • Dyspepsia (indigestion)

  • Rash


  • Alanine aminotransferase increased


  • Aspartate aminotransferase increased

  • Fractures

  • Hematuria



Uncommon (0.1-1% frequency):



  • Adrenal insufficiency

  • Myopathy

  • Rhabdomyolysis


Rare (<0.1% frequency):


  • Allergic alveolitis


Overdose


Clinical experience with overdose of abiraterone acetate is limited.[1] There is no specific antidote for abiraterone acetate overdose, and treatment should consist of general supportive measures, including monitoring of cardiac and liver function.[1]



Interactions


Abiraterone acetate is a CYP3A4 substrate and hence should not be administered concurrently with strong CYP3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone,
saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital.[24][23] It also inhibits CYP1A2, CYP2C9, and CYP3A4 and likewise should not be taken concurrently with substrates of any of these enzymes that have a narrow therapeutic index.[24][23]


Spironolactone generally exerts anti-androgenic effects, but experimental evidence exists that it acts as an androgen receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation.[25] This is supported by the observations described in several case reports.[26] Therefore, spironolactone should be avoided in prostate cancer patients suffering from treatment-associated mineralocorticoid side effects of Abiraterone acetate.



Pharmacology



Pharmacodynamics





Abiraterone, the active metabolite of abiraterone acetate.



Antiandrogenic activity


Abiraterone, the active metabolite of abiraterone acetate, inhibits CYP17A1, which manifests as two enzymes, 17α-hydroxylase (IC50 = 2.5 nM) and 17,20-lyase (IC50 = 15 nM) (approximately 6-fold more selective for inhibition of 17α-hydroxylase over 17,20-lyase)[27][28] that are expressed in testicular, adrenal, and prostatic tumor tissues. CYP17A1 catalyzes two sequential reactions: (a) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by its 17α-hydroxylase activity, and (b) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by its 17,20-lyase activity.[29] DHEA and androstenedione are androgens and precursors of testosterone. Inhibition of CYP17A1 activity by abiraterone thus decreases circulating levels of androgens such as DHEA, testosterone, and dihydrotestosterone (DHT). Abiraterone acetate, via its metabolite abiraterone, has the capacity to lower circulating testosterone levels to less than 1 ng/dL (i.e., undetectable) when added to castration.[27][30] These concentrations are considerably lower than those achieved by castration alone (~20 ng/dL).[30] The addition of abiraterone acetate to castration was found to reduce levels of DHT by 85%, DHEA by 97 to 98%, and androstenedione by 77 to 78% relative to castration alone.[30] In accordance with its antiandrogenic action, abiraterone acetate decreases the weights of the prostate gland, seminal vesicles, and testes.[31]


Abiraterone also acts as a partial antagonist of the androgen receptor (AR), and as an inhibitor of the enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11B1 (steroid 11β-hydroxylase), CYP21A2 (Steroid 21-hydroxylase), and other CYP450s (e.g., CYP1A2, CYP2C9, and CYP3A4).[24][32][33][34] In addition to abiraterone itself, part of the activity of the drug has been found to be due to a more potent active metabolite, δ4-abiraterone (D4A), which is formed from abiraterone by 3β-HSD.[35] D4A is an inhibitor of CYP17A1, 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase, and 5α-reductase, and has also been found to act as a competitive antagonist of the AR reportedly comparable to the potent antagonist enzalutamide.[35] However, the initial 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR, and promotes prostate cancer progression.[36] Its formation can be blocked by the coadministration of dutasteride, a potent and selective 5α-reductase inhibitor.[36]



Estrogenic activity


There has been interest in the use of abiraterone acetate for the treatment of breast cancer due to its ability to lower estrogen levels.[37] However, abiraterone has been found to act as a direct agonist of the estrogen receptor, and induces proliferation of human breast cancer cells in vitro.[37] If abiraterone acetate is used in the treatment of breast cancer, it should be combined with an estrogen receptor antagonist like fulvestrant.[37] In spite of its antiandrogenic and estrogenic properties, abiraterone acetate does not appear to produce gynecomastia as a side effect.[38]



Other activities


Due to inhibition of glucocorticoid biosynthesis, abiraterone acetate can cause glucocorticoid deficiency, mineralocorticoid excess, and associated adverse effects.[39] This is why the medication is combined with prednisone, a corticosteroid, which serves as a means of glucocorticoid replacement and prevents mineralocorticoid excess.[40]


Abiraterone acetate, along with galeterone, has been identified as an inhibitor of sulfotransferases (SULT2A1, SULT2B1b, SULT1E1), which are involved in the sulfation of DHEA and other endogenous steroids and compounds, with Ki values in the sub-micrmolar range.[41]



Pharmacokinetics


After oral administration, abiraterone acetate, the prodrug form in the commercial preparation, is converted into the active form, abiraterone. This conversion is likely to be esterase-mediated and not CYP-mediated. Administration with food increases absorption of the drug and thus has the potential to result in increased and highly variable exposures; the drug should be consumed on an empty stomach at least one hour before or two hours after food. The drug is highly protein bound (>99%), and is metabolised in the liver by CYP3A4 and SULT2A1 to inactive metabolites. The drug is excreted in feces (~88%) and urine (~5%), and has a terminal half-life of 12 ± 5 hours.[23]



Chemistry


See also: Steroidal antiandrogen and List of steroidal antiandrogens

Abiraterone acetate, also known as 17-(3-pyridinyl)androsta-5,16-dien-3β-ol acetate, is a synthetic androstane steroid and a derivative of androstadienol (androsta-5,16-dien-3β-ol), an endogenous androstane pheromone. It is specifically a derivative of androstadienol with a pyridine ring attached at the C17 position and an acetate ester attached to the C3β hydroxyl group. Abiraterone acetate is the C3β acetate ester of abiraterone.



History


In the early 1990s, Mike Jarman, Elaine Barrie, and Gerry Potter of the Cancer Research UK Centre for Cancer Therapeutics in the Institute of Cancer Research in London set out to develop drug treatments for prostate cancer. With the nonsteroidal androgen synthesis inhibitor ketoconazole as a model, they developed abiraterone, filing a patent in 1993 and publishing the first paper describing it the following year.[6][42] Rights for commercialization of the drug were assigned to BTG, a UK-based specialist healthcare company. BTG then licensed the product to Cougar Biotechnology, which began development of the commercial product.[43] In 2009, Cougar was acquired by Johnson & Johnson, which developed and sells the commercial product, and is conducting ongoing clinical trials to expand its clinical uses.[44]


Abiraterone acetate was approved by the United States Food and Drug Administration on April 28, 2011.[7][8] The FDA press release made reference to a phase III clinical trial in which abiraterone use was associated with a median survival of 14.8 months versus 10.9 months with placebo; the study was stopped early because of the successful outcome.[45] Abiraterone acetate was also licensed by the European Medicines Agency.[46] Until May 2012 the National Institute for Health and Clinical Excellence (NICE) did not recommend use of the drug within the NHS on cost-effectiveness grounds. This position was reversed when the manufacturer submitted revised costs.[47] The use is currently limited to men who have already received one docetaxel-containing chemotherapy regimen.[48][49]



Society and culture



Generic names


Abiraterone acetate is the generic name of the drug and its USAN, BANM, and JAN, while abiraterone is the INN and BAN of abiraterone, its deacetylated form.[10] Abiraterone acetate is also known by its developmental code names CB-7630 and JNJ-212082, while CB-7598 was the developmental code name of abiraterone.[10][50]



Brand names


Abiraterone acetate is marketed by Janssen Biotech (a subsidiary of Johnson & Johnson) under the brand name Zytiga.[10] In addition, Intas Pharmaceuticals markets the drug under the brand name Abiratas, Cadila Pharmaceuticals markets the drug as Abretone, and Glenmark Pharmaceuticals as Abirapro.[citation needed] It is marketed as Yonsa by Sun Pharmaceutical Industries (licenced from Churchill Pharmaceuticals).[5]



Availability


Abiraterone acetate is marketed widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere in Europe, Australia, New Zealand, Latin America, Asia, and Israel.[10]



Research


Abiraterone acetate is under development for the treatment of breast cancer and ovarian cancer and as of March 2018 is in phase II clinical trials for these indications.[50] It was also under investigation for the treatment of congenital adrenal hyperplasia, but no further development has been reported for this potential use.[50] An oral ultramicrosize tablet formulation of abiraterone acetate (also known as abiraterone acetate fine particle (AAFP) or submicron abiraterone acetate) with improved bioavailability is in pre-registration in the United States for the treatment of prostate cancer as of April 2018 and has the tentative brand name Yonza.[51]



See also


  • List of investigational hormonal agents § Androgenics


References





  1. ^ abcdefghijklmnopq Janssen Biotech, Inc. "ZYTIGA Prescribing Information" (PDF). Horsham, PA: U.S. Food and Drug Administration..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"""""""'""'"}.mw-parser-output .citation .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/4/4c/Wikisource-logo.svg/12px-Wikisource-logo.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}


  2. ^ abcd "Meeting Library - Meeting Library". meetinglibrary.asco.org.


  3. ^ abcd Benoist GE, Hendriks RJ, Mulders PF, Gerritsen WR, Somford DM, Schalken JA, van Oort IM, Burger DM, van Erp NP (November 2016). "Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide". Clin Pharmacokinet. 55 (11): 1369–1380. doi:10.1007/s40262-016-0403-6. PMC 5069300. PMID 27106175.


  4. ^ Potter et al. J. Med. Chem., 1995, 38 (13), pp 2463–2471


  5. ^ ab Sun Pharma Gets FDA Go-Ahead for Yonsa for Prostate Cancer May 2018


  6. ^ ab Scowcroft H (2011-09-21). "Where did abiraterone come from?". Cancer Research UK. Retrieved 2011-09-28.


  7. ^ ab "Drugs@FDA - FDA Approved Drug Products - Zytiga". www.fda.gov. United States Food and Drug Administration. Retrieved 4 March 2016.


  8. ^ ab "FDA approves Zytiga for late-stage prostate cancer" (Press release). United States Food and Drug Administration. 2011-04-28.


  9. ^ NCI Staff. "Abiraterone Approved for Earlier Use in Men with Metastatic Prostate Cancer". U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute.


  10. ^ abcde "Abiraterone". Drugs.com.


  11. ^ "Generic Zytiga Availability". Drugs.com.


  12. ^ abc "Zytiga (abiraterone acetate) tablet [Janssen Biotech, Inc.]". DailyMed. Janssen Biotech, Inc. September 2013. Retrieved 24 January 2014.


  13. ^ abcd "Zytiga: EPAR - Product Information" (PDF). European Medicines Agency. Janssen-Cilag International N.V. 29 October 2013. Retrieved 24 January 2014.


  14. ^ abc "Zytiga 250 mg tablets - Summary of Product Characteristics". electronic Medicines Compendium. Janssen-Cilag Ltd. 21 January 2014. Archived from the original on 2014-02-01. Retrieved 24 January 2014.


  15. ^ abc "Zytiga abiraterone acetate product information" (PDF). TGA eBusiness Services. Janssen-Cilag Pty Ltd. 1 March 2012. Retrieved 24 January 2014.


  16. ^ "Pharmaceutical Benefits Scheme - Abiraterone". Pharmaceutical Benefits Scheme. Retrieved 24 January 2014.


  17. ^ Pokuri VK, Nourkeyhani H, Betsy B, Herbst L, Sikorski M, Spangenthal E, Fabiano A, George S (July 2015). "Strategies to Circumvent Testosterone Surge and Disease Flare in Advanced Prostate Cancer: Emerging Treatment Paradigms". J Natl Compr Canc Netw. 13 (7): e49–55. doi:10.6004/jnccn.2015.0109. PMID 26150586.


  18. ^ Clinical trial number NCT00638690 for "Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy" at ClinicalTrials.gov


  19. ^ de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI (May 2011). "Abiraterone and increased survival in metastatic prostate cancer". The New England Journal of Medicine. 364 (21): 1995–2005. doi:10.1056/NEJMoa1014618. PMC 3471149. PMID 21612468.


  20. ^ Clinical trial number NCT00887198 for "Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer" at ClinicalTrials.gov


  21. ^ "BTG and Ortho Biotech's Prostate Cancer Trial Unblinded". Genetic Engineering & Biotechnology News. 2010-09-10. Retrieved 2011-05-26.


  22. ^ Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE (January 2013). "Abiraterone in metastatic prostate cancer without previous chemotherapy". The New England Journal of Medicine. 368 (2): 138–48. doi:10.1056/NEJMoa1209096. PMC 3683570. PMID 23228172.


  23. ^ abcde "Zytiga prescribing information" (PDF). Janssen Biotech. May 2012. Archived from the original (pdf) on 2014-11-13. Retrieved 4 March 2016.


  24. ^ abcde "Zytiga (abiraterone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.


  25. ^ Luthy IA, Begin DJ, Labrie F (November 1988). "Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture". Journal of Steroid Biochemistry. 31 (5): 845–52. doi:10.1016/0022-4731(88)90295-6. PMID 2462135.


  26. ^ Dhondt B, Buelens S, Van Besien J, Beysens M, De Bleser E, Ost P, Lumen N (November 2018). "Abiraterone and spironolactone in prostate cancer: a combination to avoid". Acta Clinica Belgica: 1–6. doi:10.1080/17843286.2018.1543827. PMID 30477405.


  27. ^ ab Neidle S (30 September 2013). Cancer Drug Design and Discovery. Academic Press. pp. 341–342. ISBN 978-0-12-397228-6.


  28. ^ Fernández-Cancio M, Camats N, Flück CE, Zalewski A, Dick B, Frey BM, Monné R, Torán N, Audí L, Pandey AV (April 2018). "Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency". Pharmaceuticals. 11 (2): 37. doi:10.3390/ph11020037. PMID 29710837.


  29. ^ Attard G, Belldegrun AS, de Bono JS (December 2005). "Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer". BJU International. 96 (9): 1241–6. doi:10.1111/j.1464-410X.2005.05821.x. PMID 16287438.


  30. ^ abc Small EJ (November 2014). "Can targeting the androgen receptor in localized prostate cancer provide insights into why men with metastatic castration-resistant prostate cancer die?". Journal of Clinical Oncology. 32 (33): 3689–91. doi:10.1200/JCO.2014.57.8534. PMID 25311216. Abiraterone acetate is a prodrug for abiraterone, a CYP17 inhibitor, which has the capacity to lower serum testosterone levels to less than 1 ng/dL (compared with levels closer to 20 ng/dL that are achieved with conventional ADT).19 [...] Relative to LHRHa alone, the addition of abiraterone resulted in an 85% decline in dihydrotestosterone (DHT) levels, a 97% to 98% decline in dehydroepiandrosterone (DHEA) levels, and a 77% to 78% decline in androstenedione levels.


  31. ^ Tindall DJ, James M (20 April 2009). Androgen Action in Prostate Cancer. Springer Science & Business Media. pp. 748–. ISBN 978-0-387-69179-4.


  32. ^ Yin L, Hu Q (January 2014). "CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents". Nature Reviews. Urology. 11 (1): 32–42. doi:10.1038/nrurol.2013.274. PMID 24276076.


  33. ^ Malikova J, Brixius-Anderko S, Udhane SS, Parween S, Dick B, Bernhardt R, Pandey AV (November 2017). "CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2". The Journal of Steroid Biochemistry and Molecular Biology. 174: 192–200. doi:10.1016/j.jsbmb.2017.09.007. PMID 28893623.


  34. ^ Udhane SS, Dick B, Hu Q, Hartmann RW, Pandey AV (September 2016). "Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis". Biochemical and Biophysical Research Communications. 477 (4): 1005–1010. doi:10.1016/j.bbrc.2016.07.019. PMID 27395338.


  35. ^ ab Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, Liu J, Upadhyay SK, Auchus RJ, Sharifi N (July 2015). "Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer". Nature. 523 (7560): 347–51. doi:10.1038/nature14406. PMC 4506215. PMID 26030522.


  36. ^ ab Li Z, Alyamani M, Li J, Rogacki K, Abazeed M, Upadhyay SK, Balk SP, Taplin ME, Auchus RJ, Sharifi N (May 2016). "Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy" (PDF). Nature. 533 (7604): 547–51. doi:10.1038/nature17954. PMID 27225130.


  37. ^ abc Capper CP, Larios JM, Sikora MJ, Johnson MD, Rae JM (May 2016). "The CYP17A1 inhibitor abiraterone exhibits estrogen receptor agonist activity in breast cancer". Breast Cancer Research and Treatment. 157 (1): 23–30. doi:10.1007/s10549-016-3774-3. PMID 27083183.


  38. ^ Alesini D, Iacovelli R, Palazzo A, Altavilla A, Risi E, Urbano F, Manai C, Passaro A, Magri V, Cortesi E (2013). "Multimodality treatment of gynecomastia in patients receiving antiandrogen therapy for prostate cancer in the era of abiraterone acetate and new antiandrogen molecules". Oncology. 84 (2): 92–9. doi:10.1159/000343821. PMID 23128186.


  39. ^ Figg WD, Chau CH, Small EJ (14 September 2010). Drug Management of Prostate Cancer. Springer Science & Business Media. p. 97. ISBN 978-1-60327-829-4.


  40. ^ Rosenthal L, Burchum J (17 February 2017). Lehne's Pharmacotherapeutics for Advanced Practice Providers - E-Book. Elsevier Health Sciences. p. 936. ISBN 978-0-323-44779-9.


  41. ^ Yip CK, Bansal S, Wong SY, Lau AJ (April 2018). "Identification of Galeterone and Abiraterone as Inhibitors of Dehydroepiandrosterone Sulfonation Catalyzed by Human Hepatic Cytosol, SULT2A1, SULT2B1b, and SULT1E1". Drug Metabolism and Disposition. 46 (4): 470–482. doi:10.1124/dmd.117.078980. PMID 29436390.


  42. ^ "A new way to treat prostate cancer: The story of abiraterone". The Institute of Cancer Research. 2012-09-10. Retrieved 2012-11-12.


  43. ^ "Abiraterone Acetate (CB7630)". Cougar Biotechnology. Archived from the original on 2008-09-07. Retrieved 2008-08-20.


  44. ^ "Johnson & Johnson Announces Definitive Agreement to Acquire Cougar Biotechnology, Inc" (Press release). Cougar Biotechnology. 2009-05-11. Archived from the original on 2009-05-29. Retrieved 2009-06-03.


  45. ^ "FDA Approval for Abiraterone Acetate". U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute.


  46. ^ "EMA assessment of Zytiga (abiraterone)". European Medicines Agency.


  47. ^ "Prostate cancer (metastatic, castration resistant) - abiraterone (following cytoxic therapy): final appraisal determination guidance" (PDF). NICE guidance. 15 May 2012. Archived from the original (PDF) on February 19, 2013.


  48. ^ "NICE technology appraisal guidance [TA259]". NICE guidance. June 2012.


  49. ^ "NICE appraisal of earlier treatment with abiraterone for prostate cancer". NICE press release. 14 August 2014.


  50. ^ abc "Abiraterone acetate - Johnson & Johnson". Adis Insight.


  51. ^ "Abiraterone acetate - Churchill Pharmaceuticals". Adis Insight.




External links



  • Zytiga (abiraterone acetate) - Official website

  • Abiraterone acetate - AdisInsight











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