سیپروترون استات

سیپروترون استات (به انگلیسی: Cyproterone acetate) (CPA)، به تنهایی با نام تجاری Androcur یا با اتینیل‌استرادیول با نام‌های تجاری Diane یا Diane-35 و دیگر نام‌ها فروخته می‌شود، یک داروی ضدآندروژن و پروژستین است که در درمان شرایط وابسته به آندروژن مانند آکنه، رشد بیش از حد مو، بلوغ زودرس، سرطان پروستات و به عنوان مولفه‌ای در هورمون‌درمانی زنانه‌سازی برای زنان تراجنسی، و همچنین در قرص‌های ضدبارداری خوراکی استفاده می‌شود.^{[13][14][15][16][17]} این ماده به تنهایی یا در ترکیب با استروژن فرموله و استفاده می‌شود و برای استفاده به صورت خوراکی در دسترس است. CPA روزانه یک تا سه بار و به شکل خوراکی مصرف می‌شود.

سیپروترون استات

داده‌های بالینی
نام‌های تجاری	Androcur, Androcur Depot, Cyprostat, Siterone, others
نام‌های دیگر	SH-80714; SH-714; NSC-81430; 1α,2α-Methylene-6-chloro-17α-hydroxy-δ6-progesterone acetate; 1α,2α-Methylene-6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione acetate
AHFS/Drugs.com	Micromedex Detailed Consumer Information
رده‌بندی داروهای بارداری	X
روش مصرف دارو	خوراکی، تزریق عضلانی
گروه دارویی	Steroidal antiandrogen; Progestogen; Progestin; Progestogen ester; Antigonadotropin
کد ATC	G03HA01
وضعیت قانونی
وضعیت قانونی	℞ (Prescription only)
داده‌های فارماکوکینتیک
زیست فراهمی	خوراکی: ۶۸–۱۰۰٪[1][2]
پیوند پروتئینی	آلبومین (دارو): ۹۳٪ آزاد: ۷٪[3][4][5][6]
متابولیسم	کبد (CYP3A4)[7][8]
متابولیت‌ها	• 15β-OH-CPA (عمده)[1][9] • سیپروترون (جزئی)[10] • استیک اسید (جزئی)[10]
نیمه‌عمر حذف	خوراکی: ۱٫۶–۴٫۳ روز[10][11][12] IM: ۳–۴٫۳ روز[2][10][12]
دفع	مدفوع: ۷۰٪[10] ادرار: ۳۰٪[10]
شناسه‌ها
نام آیوپاک (2aR,3aS,3bS,3cS,5aS,6R,8aS,8bR)-6-acetyl-10-chloro-3b,5a-dimethyl-2-oxo-2,2a,3,3a,3b,3c,4,5,5a,6,7,8,8a,8b-tetradecahydrocyclopenta[a]cyclopropa[g]phenanthren-6-yl acetate
شمارهٔ سی‌ای‌اس	427-51-0 Y 2098-66-0 (سیپروترون)
پاب‌کم CID	9880
IUPHAR/BPS	2865
دراگ‌بنک	DB04839
کم‌اسپایدر	9496 Y
UNII	4KM2BN5JHF
KEGG	D01368
ChEBI	CHEBI:50743 Y
ChEMBL	ChEMBL139835 Y
CompTox Dashboard (EPA)	DTXSID5020366
ECHA InfoCard	100.006.409
داده‌های فیزیکی و شیمیایی
فرمول شیمیایی	C24H29ClO4
جرم مولی	۷۰۰۲۴۱۶۹۴۰۰۰۰۰۰۰۰۰۰♠۴۱۶٫۹۴ g·mol−1
مدل سه بعدی (جی‌مول)	Interactive image
نقطه ذوب	۲۰۰ تا[ابزار تبدیل: یکای ناشناخته]
SMILES CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)[C@@H]5C[C@@H]5[C@]34C)Cl)C)OC(=O)C
InChI InChI=1S/C24H29ClO4/c1-12(26)24(29-13(2)27)8-6-16-14-10-20(25)19-11-21(28)15-9-18(15)23(19,4)17(14)5-7-22(16,24)3/h10-11,14-18H,5-9H2,1-4H3/t14-,15+,16-,17-,18-,22-,23-,24-/m0/s1 Key:UWFYSQMTEOIJJG-FDTZYFLXSA-N
(صحت‌سنجی)

سنتز

روش‌هایی جهت سنتز شیمیایی CPA ابداع شده‌است.^[18][19][20] در زیر یکی از این روش‌های سنتز آورده شده‌است:^[21][22]

سنتز جزئی CPA، با استفاده از هیدروکسی‌پروژسترون استات به عنوان ماده اولیه، توسط Wiechert & Neumann (1965) و Wiechert (1966).^[21][22]

منابع

2. Huber J, Zeillinger R, Schmidt J, Täuber U, Kuhnz W, Spona J (November 1988). "Pharmacokinetics of cyproterone acetate and its main metabolite 15 beta-hydroxy-cyproterone acetate in young healthy women". Int J Clin Pharmacol Ther Toxicol. 26 (11): 555–61. PMID 2977383.
3. Bińkowska M, Woroń J (June 2015). "Progestogens in menopausal hormone therapy". Przegla̜d Menopauzalny = Menopause Review. 14 (2): 134–43. doi:10.5114/pm.2015.52154. PMC 4498031. PMID 26327902.
4. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (December 2003). "Classification and pharmacology of progestins" (PDF). Maturitas. 46 Suppl 1: S7–S16. doi:10.1016/j.maturitas.2003.09.014. PMID 14670641. Since there is no binding of CPA to SHBG and CBG in the serum, 93% of the compound is bound to serum albumin.^{[پیوند مرده]}
5. Wakelin, Sarah H.; Maibach, Howard I.; Archer, Clive B. (1 June 2002). Systemic Drug Treatment in Dermatology: A Handbook. CRC Press. pp. 32–. ISBN 978-1-84076-013-2. It is almost exclusively bound to plasma albumin.
6. Hammond GL, Lähteenmäki PL, Lähteenmäki P, Luukkainen T (October 1982). "Distribution and percentages of non-protein bound contraceptive steroids in human serum". Journal of Steroid Biochemistry. 17 (4): 375–80. doi:10.1016/0022-4731(82)90629-X. PMID 6215538.
7. Dickman, Andrew (27 September 2012). Drugs in Palliative Care. OUP Oxford. pp. 137–138. ISBN 978-0-19-966039-1.
8. Boarder, Michael; Newby, David; Navti, Phyllis (25 March 2010). Pharmacology for Pharmacy and the Health Sciences: A Patient-centred Approach. OUP Oxford. pp. 632–. ISBN 978-0-19-955982-4.
9. Frith RG, Phillipou G (1985). "15-Hydroxycyproterone acetate and cyproterone acetate levels in plasma and urine". J. Chromatogr. 338 (1): 179–86. doi:10.1016/0378-4347(85)80082-7. PMID 3160716.
10. Georg F. Weber (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 316–. ISBN 978-3-319-13278-5. The terminal half-life is about 38 h. A portion of the drug is metabolized by hydrolysis to cyproterone and acetic acid. However, in contrast to many other steroid esters hydrolysis is not extensive, and much of the pharmacological activity is exerted by the acetate form. Excretion is about 70% in the feces, mainly in the form of glucuronidated metabolites, and about 30% in the urine, predominantly as non-conjugated metabolites.
12. AAPL Newsletter (PDF). The Academy. 1998. CPA is 100% bioavailable when taken orally with a half life of 38 hours. The injectable form reaches maximum plasma levels in 82 hours and has a half life of about 72 hours.
13. Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
14. Barradell LB, Faulds D (July 1994). "Cyproterone. A review of its pharmacology and therapeutic efficacy in prostate cancer". Drugs Aging. 5 (1): 59–80. doi:10.2165/00002512-199405010-00006. PMID 7919640.
15. Neumann F (1994). "The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research". Exp. Clin. Endocrinol. 102 (1): 1–32. doi:10.1055/s-0029-1211261. PMID 8005205.
16. Neumann F (January 1977). "Pharmacology and potential use of cyproterone acetate". Horm. Metab. Res. 9 (1): 1–13. doi:10.1055/s-0028-1093574. PMID 66176.
17. Neumann F, Töpert M (November 1986). "Pharmacology of antiandrogens". Journal of Steroid Biochemistry. 25 (5B): 885–95. doi:10.1016/0022-4731(86)90320-1. PMID 2949114.
18. Jürgen Engel; Axel Kleemann; Bernhard Kutscher; Dietmar Reichert (14 May 2014). Pharmaceutical Substances, 5th Edition, 2009: Syntheses, Patents and Applications of the most relevant APIs. Thieme. pp. 351–352. ISBN 978-3-13-179275-4.
19. William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 1182–1183. ISBN 978-0-8155-1856-3.
20. Duang Buddhasukh, Roland Maier, Aranya Manosroi, Jiradej Manosroi, Pattana Sripalakit, Rolf Werner (29 April 2002). "EP1359154A1 Further syntheses of cyproterone acetate". Google Patents.{{cite web}}: نگهداری یادکرد:استفاده از پارامتر نویسندگان (link)
21. "Verfahren zur Herstellung von 1, 2alpha-Methylen-delta-17alpha-hydroxy-progesteronen"."Verfahren zur Herstellung von 1, 2alpha-Methylen-delta-17alpha-hydroxy-progesteronen".
22. "6-chloro-1, 2alpha-methylene-delta6-17alpha-hydroxyprogesterone compounds and compositions"."6-chloro-1, 2alpha-methylene-delta6-17alpha-hydroxyprogesterone compounds and compositions".

مطالعه بیشتر

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• Gräf, K. -J.; Brotherton, J.; Neumann, F. (1974). Androgens II and Antiandrogens / Androgene II und Antiandrogene. pp. 485–542. doi:10.1007/978-3-642-80859-3_7. ISBN 978-3-642-80861-6.
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