青黴胺

青黴胺
臨床資料
商品名（英語：Drug nomenclature）	Cuprimine, Cuprenyl, Depen
其他名稱	D-penicillamine
AHFS/Drugs.com	Monograph
MedlinePlus	a618021
核准狀況	美 DailyMed: Penicillamine;
懷孕分級	澳: D ; ;
給藥途徑	By mouth (capsules)
ATC碼	M01CC01 (WHO) ;
法律規範狀態
法律規範	美：處方藥（℞-only）; 處方藥（℞-only）;
藥物動力學數據
生物利用度	Variable
藥物代謝	Liver
生物半衰期	1小時
排泄途徑	Kidney
識別資訊
	IUPAC命名法 (2S)-2-amino-3-methyl-3-sulfanylbutanoic acid; ;
CAS號	52-67-5
PubChem CID	5852;
IUPHAR/BPS	7264;
DrugBank	DB00859 ;
ChemSpider	5643 ;
UNII	GNN1DV99GX;
KEGG	D00496 ;
ChEBI	CHEBI:7959 ;
ChEMBL	ChEMBL1430 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID6037069 ;
ECHA InfoCard	100.000.136
化學資訊
化學式	C5H11NO2S
摩爾質量	149.21 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES CC(C)([C@H](C(=O)O)N)S;
	InChI InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1 ; Key:VVNCNSJFMMFHPL-VKHMYHEASA-N ;

青黴胺，以Cuprimine品牌銷售，是一種主要用於治療威爾遜氏病的口服藥物^[1] ^[2]，還用於患有尿胱氨酸水平高、類風濕性關節炎以及各種重金屬中毒的腎結石患者^[1]^[2]。

Quick Facts 臨床資料, 商品名（英語：Drug nomenclature） ...

Close

美國 1970 年批准青黴胺用於醫療用途，並且在世界衛生組織的基本藥物清單上^[1] ^[3]。

青黴胺可以用作螯合劑於：

威爾遜氏病（一種罕見的銅代謝遺傳病）中，青黴胺與積累的銅的結合併通過尿液消除進行治療。 ^[4]
青黴胺是繼二巰基丙醇(BAL)之後治療砷中毒的二線藥物 ^[5]，已經不再推薦使用 ^[6]。

在胱氨酸尿症（一種遺傳性疾病，其中高尿胱氨酸水平導致胱氨酸結石形成）中，青黴胺可以與半胱氨酸結合產生比胱氨酸更易溶解的混合二硫化物。^[7]

青黴胺可以用於治療硬皮病。 ^[8]

對常規療法的充分試驗沒有反應的嚴重活動性類風濕性關節炎患者，青黴胺可用作緩解疾病的抗風濕藥(DMARD) 進行治療 ^[9]。儘管由於 TNF 抑制劑、托珠單抗和托法替尼的使用，青黴胺如今已經較少使用。青黴胺通過減少T淋巴細胞數量、抑制巨噬細胞功能、減少IL-1 、減少類風濕因子和防止膠原交聯來起作用。

骨髓抑制、味覺障礙、厭食、嘔吐和腹瀉是最常見的副作用，約 20-30% 接受青黴胺治療的患者會產生，青黴胺常見的副作用還包括皮疹以及白血球減少。^[10]^[11]^[1]其他嚴重的副作用包括肝病、閉塞性細支氣管炎和重症肌無力，^[1]並且不建議紅斑狼瘡患者使用青黴胺， ^[2]懷孕期間使用也可能會對嬰兒造成傷害^[2]。

其他可能的不良反應包括：

腎病^[7]^[11]
肝毒性^[12]
膜性腎小球腎炎^[13]
再生不良性貧血（特異質性） ^[12]
抗體介導的重症肌無力^[11]和藍伯-伊頓肌無力症候群，即使停藥後仍可能持續存在
藥物性系統性紅斑狼瘡^[14]
匐行性穿孔性彈性組織變性^[15]
中毒性肌病^[16]
乳房脹大^[17]
少精症

D-(–)-(S)-青黴胺（有抗關節炎作用）

L-(+)-(R)-青黴胺（有毒）

青黴胺對映體

青黴胺是一種三官能有機化合物，由硫醇、胺和羧酸組成，結構上類似於 α-胺基酸半胱氨酸，但在硫醇上有孿生二甲基取代基。像大多數胺基酸一樣，是一種無色固體，在生理pH值下以兩性離子的形式存在。

青黴胺是一種手性藥物，具有一個立體中心，以一對對映異構體的形式存在，如圖所示。 (S)對映異構體，具有抗關節炎作用，L-青黴胺（R絕對構型）是有毒的，因為它會抑制吡哆醇（即維生素B₆ ）起作用。^[18] ^[19]該對映異構體是青黴素的代謝物，但本身沒有抗生素特性。 ^[20]多種青黴胺-銅複合結構已知。 ^[21]

John Walshe於1956年首次描述了青黴胺在威爾遜病中的使用。 ^[22]他在服用青黴素的患者（包括他自己）的尿液中發現了這種化合物，並通過實驗證實它通過螯合作用增加了尿銅的排泄。他最初難以說服當時的幾位世界專家（丹尼·布朗和卡明斯），因為其他人認為威爾遜病的主要問題不在於銅穩態，而是胺基酸代謝問題，並且應該使用二巰基丙醇作為螯合劑。後來經研究證實了以銅-中心理論和D-青黴胺的功效。 Walshe 還率先在 Wilson 開創了其他的螯合劑如三亞乙基四胺和四硫代鉬酸鹽。 ^[23]

青黴胺首先由約翰·康福斯在羅伯特·羅賓遜的監督下合成。 ^[24]

1964 年出現第一個成功案例以來，青黴胺一直用於治療類風濕性關節炎。 ^[25]

在美國，Valeant在2016年將藥物成本從每月約500美元提高到24,000美元。 ^[26]

[1]
Penicillamine. The American Society of Health-System Pharmacists. [8 December 2016]. （原始內容存檔於21 December 2016）.
[2]
WHO Model Formulary 2008. 2009: 64, 592. ISBN 9789241547659.World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. pp. 64, 592. hdl:10665/44053. ISBN 9789241547659.
[3]
World Health Organization model list of essential medicines: 21st list 2019. Geneva. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
[4]
Peisach, J.; Blumberg, W. E. A mechanism for the action of penicillamine in the treatment of Wilson's disease. Molecular Pharmacology. 1969, 5 (2): 200–209. PMID 4306792.
[5]
Peterson, R. G.; Rumack, B. H. D-Penicillamine therapy of acute arsenic poisoning. The Journal of Pediatrics. 1977, 91 (4): 661–666. PMID 908992. doi:10.1016/S0022-3476(77)80528-3.
[6]
Hall, A. H. Chronic arsenic poisoning. Toxicology Letters. 2002, 128 (1–3): 69–72. PMID 11869818. doi:10.1016/S0378-4274(01)00534-3.
[7]
Rosenberg, L. E.; Hayslett, J. P. Nephrotoxic Effects of Penicillamine in Cystinuria. JAMA: The Journal of the American Medical Association. 1967, 201 (9): 698–9. PMID 6071831. doi:10.1001/jama.1967.03130090062021.Rosenberg, L. E.; Hayslett, J. P. (1967). "Nephrotoxic Effects of Penicillamine in Cystinuria". JAMA: The Journal of the American Medical Association. 201 (9): 698–9. doi:10.1001/jama.1967.03130090062021. PMID 6071831.
[8]
Steen, V. D.; Medsger Jr, T. A.; Rodnan, G. P. D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): A retrospective analysis. Annals of Internal Medicine. 1982, 97 (5): 652–659. PMID 7137731. doi:10.7326/0003-4819-97-5-652.
[9]
Cuprimine (penicillamine) Capsules for Oral Use. U.S. Full Prescribing Information (PDF). [29 April 2016]. （原始內容 (PDF)存檔於8 September 2015）.
[10]
Grasedyck, K. D-Penicillamine—side effects, pathogenesis and decreasing the risks. Zeitschrift für Rheumatologie. 1988,. 47 Suppl 1: 17–19. PMID 3063003.
[11]
Camp, A. V. Penicillamine in the treatment of rheumatoid arthritis. Proceedings of the Royal Society of Medicine. 1977, 70 (2): 67–69. PMC 1542978 . PMID 859814. doi:10.1177/003591577707000201.Camp, A. V. (1977). "Penicillamine in the treatment of rheumatoid arthritis". Proceedings of the Royal Society of Medicine. 70 (2): 67–69. doi:10.1177/003591577707000201. PMC 1542978. PMID 859814.
[12]
Fishel, B.; Tishler, M.; Caspi, D.; Yaron, M. Fatal aplastic anaemia and liver toxicity caused by D-penicillamine treatment of rheumatoid arthritis. Annals of the Rheumatic Diseases. 1989, 48 (7): 609–610. PMC 1003826 . PMID 2774703. doi:10.1136/ard.48.7.609.
[13]
Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology 8th. Philadelphia: Saunders. 2007. ISBN 978-1-4160-2973-1.
[14]
Chalmers, A.; Thompson, D.; Stein, H. E.; Reid, G.; Patterson, A. C. Systemic lupus erythematosus during penicillamine therapy for rheumatoid arthritis. Annals of Internal Medicine. 1982, 97 (5): 659–663. PMID 6958210. doi:10.7326/0003-4819-97-5-659.
[15]
Bolognia, Jean; et al. Dermatology. Philadelphia: Elsevier. 2007. ISBN 978-1-4160-2999-1.2nd edition.
[16]
Underwood, J. C. E. General and Systemic Pathology. Elsevier Limited. 2009. ISBN 978-0-443-06889-8.
[17]
Taylor; Cumming; Corenblum. Successful treatment of D-penicillamine-induced breast gigantism with danazol. Br Med J. January 31, 1981, 282 (6261): 362–3. PMC 1504185 . PMID 6780026. doi:10.1136/bmj.282.6261.362-a.
[18]
Ariens, E.J. Chiral Separations by HPLC. Chichester: Ellis Horwwod, Chichester. 1989: 31–68.
[19]
Aronson, J. K. Meyler's Side Effects of Analgesics and Anti-inflammatory Drugs. Amsterdam: Elsevier Science. 2010: 613. ISBN 9780080932941. （原始內容存檔於2017-09-10）.
[20]
Parker, C. W.; Shapiro, J.; Kern, M.; Eisen, H. N. Hypersensitivity to penicillenic acid derivatives in human beings with penicillin allergy. The Journal of Experimental Medicine. 1962, 115 (4): 821–838. PMC 2137514 . PMID 14483916. doi:10.1084/jem.115.4.821.
[21]
Birker, Paul J. M. W. L.; Freeman, Hans C. Structure, properties, and function of a copper(I)–copper(II) complex of D-penicillamine: pentathallium(I) μ₈-chloro-dodeca(D-penicillaminato)octacuprate(I)hexacuprate(II) n-hydrate. J. Am. Chem. Soc. 1977, 99 (21): 6890–6899. PMID 903530. doi:10.1021/ja00463a019.
[22]
Walshe, J. M. Wilson's disease; new oral therapy. Lancet. Jan 1956, 270 (6906): 25–6. PMID 13279157. doi:10.1016/S0140-6736(56)91859-1.
[23]
Walshe, J. M. The Story of Penicillamine: a Difficult Birth. Mov. Disord. Aug 2003, 18 (8): 853–9. PMID 12889074. doi:10.1002/mds.10458.
[24]
Oakes, Elizabeth H. Encyclopedia of World Scientists. Infobase Publishing. 2007: 156 [2021-10-18]. ISBN 9781438118826. （原始內容存檔於2021-10-18）.
[25]
Jaffe, I. A. Rheumatoid Arthritis with Arteritis; Report of a Case Treated with Penicillamine. Annals of Internal Medicine. 1964, 61: 556–563. PMID 14218939. doi:10.7326/0003-4819-61-3-556.
[26]
Petersen, Melody. How 4 drug companies rapidly raised prices on life-saving drugs. Los Angeles Times. [27 March 2019]. （原始內容存檔於2019-03-27）.

Penicillamine. Drug Information Portal. U.S. National Library of Medicine. [2021-10-18]. （原始內容存檔於2019-12-05）.

[AHFS2016-1] [1]
Penicillamine. The American Society of Health-System Pharmacists. [8 December 2016]. （原始內容存檔於21 December 2016）.

[WHO2008-2] [2]
WHO Model Formulary 2008. 2009: 64, 592. ISBN 9789241547659.World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. pp. 64, 592. hdl:10665/44053. ISBN 9789241547659.

[WHO21st-3] [3]
World Health Organization model list of essential medicines: 21st list 2019. Geneva. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

[xl2-4] [4]
Peisach, J.; Blumberg, W. E. A mechanism for the action of penicillamine in the treatment of Wilson's disease. Molecular Pharmacology. 1969, 5 (2): 200–209. PMID 4306792.

[5] [5]
Peterson, R. G.; Rumack, B. H. D-Penicillamine therapy of acute arsenic poisoning. The Journal of Pediatrics. 1977, 91 (4): 661–666. PMID 908992. doi:10.1016/S0022-3476(77)80528-3.

[6] [6]
Hall, A. H. Chronic arsenic poisoning. Toxicology Letters. 2002, 128 (1–3): 69–72. PMID 11869818. doi:10.1016/S0378-4274(01)00534-3.

[xl4-7] [7]
Rosenberg, L. E.; Hayslett, J. P. Nephrotoxic Effects of Penicillamine in Cystinuria. JAMA: The Journal of the American Medical Association. 1967, 201 (9): 698–9. PMID 6071831. doi:10.1001/jama.1967.03130090062021.Rosenberg, L. E.; Hayslett, J. P. (1967). "Nephrotoxic Effects of Penicillamine in Cystinuria". JAMA: The Journal of the American Medical Association. 201 (9): 698–9. doi:10.1001/jama.1967.03130090062021. PMID 6071831.

[8] [8]
Steen, V. D.; Medsger Jr, T. A.; Rodnan, G. P. D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): A retrospective analysis. Annals of Internal Medicine. 1982, 97 (5): 652–659. PMID 7137731. doi:10.7326/0003-4819-97-5-652.

[PI-9] [9]
Cuprimine (penicillamine) Capsules for Oral Use. U.S. Full Prescribing Information (PDF). [29 April 2016]. （原始內容 (PDF)存檔於8 September 2015）.

[10] [10]
Grasedyck, K. D-Penicillamine—side effects, pathogenesis and decreasing the risks. Zeitschrift für Rheumatologie. 1988,. 47 Suppl 1: 17–19. PMID 3063003.

[xl3-11] [11]
Camp, A. V. Penicillamine in the treatment of rheumatoid arthritis. Proceedings of the Royal Society of Medicine. 1977, 70 (2): 67–69. PMC 1542978 . PMID 859814. doi:10.1177/003591577707000201.Camp, A. V. (1977). "Penicillamine in the treatment of rheumatoid arthritis". Proceedings of the Royal Society of Medicine. 70 (2): 67–69. doi:10.1177/003591577707000201. PMC 1542978. PMID 859814.

[xl-12] [12]
Fishel, B.; Tishler, M.; Caspi, D.; Yaron, M. Fatal aplastic anaemia and liver toxicity caused by D-penicillamine treatment of rheumatoid arthritis. Annals of the Rheumatic Diseases. 1989, 48 (7): 609–610. PMC 1003826 . PMID 2774703. doi:10.1136/ard.48.7.609.

[Kumar8-5-13] [13]
Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology 8th. Philadelphia: Saunders. 2007. ISBN 978-1-4160-2973-1.

[14] [14]
Chalmers, A.; Thompson, D.; Stein, H. E.; Reid, G.; Patterson, A. C. Systemic lupus erythematosus during penicillamine therapy for rheumatoid arthritis. Annals of Internal Medicine. 1982, 97 (5): 659–663. PMID 6958210. doi:10.7326/0003-4819-97-5-659.

[15] [15]
Bolognia, Jean; et al. Dermatology. Philadelphia: Elsevier. 2007. ISBN 978-1-4160-2999-1.2nd edition.

[16] [16]
Underwood, J. C. E. General and Systemic Pathology. Elsevier Limited. 2009. ISBN 978-0-443-06889-8.

[17] [17]
Taylor; Cumming; Corenblum. Successful treatment of D-penicillamine-induced breast gigantism with danazol. Br Med J. January 31, 1981, 282 (6261): 362–3. PMC 1504185 . PMID 6780026. doi:10.1136/bmj.282.6261.362-a.

[18] [18]
Ariens, E.J. Chiral Separations by HPLC. Chichester: Ellis Horwwod, Chichester. 1989: 31–68.

[19] [19]
Aronson, J. K. Meyler's Side Effects of Analgesics and Anti-inflammatory Drugs. Amsterdam: Elsevier Science. 2010: 613. ISBN 9780080932941. （原始內容存檔於2017-09-10）.

[sb-20] [20]
Parker, C. W.; Shapiro, J.; Kern, M.; Eisen, H. N. Hypersensitivity to penicillenic acid derivatives in human beings with penicillin allergy. The Journal of Experimental Medicine. 1962, 115 (4): 821–838. PMC 2137514 . PMID 14483916. doi:10.1084/jem.115.4.821.

[21] [21]
Birker, Paul J. M. W. L.; Freeman, Hans C. Structure, properties, and function of a copper(I)–copper(II) complex of D-penicillamine: pentathallium(I) μ₈-chloro-dodeca(D-penicillaminato)octacuprate(I)hexacuprate(II) n-hydrate. J. Am. Chem. Soc. 1977, 99 (21): 6890–6899. PMID 903530. doi:10.1021/ja00463a019.

[Walshe1956-22] [22]
Walshe, J. M. Wilson's disease; new oral therapy. Lancet. Jan 1956, 270 (6906): 25–6. PMID 13279157. doi:10.1016/S0140-6736(56)91859-1.

[23] [23]
Walshe, J. M. The Story of Penicillamine: a Difficult Birth. Mov. Disord. Aug 2003, 18 (8): 853–9. PMID 12889074. doi:10.1002/mds.10458.

[24] [24]
Oakes, Elizabeth H. Encyclopedia of World Scientists. Infobase Publishing. 2007: 156 [2021-10-18]. ISBN 9781438118826. （原始內容存檔於2021-10-18）.

[25] [25]
Jaffe, I. A. Rheumatoid Arthritis with Arteritis; Report of a Case Treated with Penicillamine. Annals of Internal Medicine. 1964, 61: 556–563. PMID 14218939. doi:10.7326/0003-4819-61-3-556.

[26] [26]
Petersen, Melody. How 4 drug companies rapidly raised prices on life-saving drugs. Los Angeles Times. [27 March 2019]. （原始內容存檔於2019-03-27）.

[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]

[26]

Wikiwand in your browser!

青黴胺

Wikiwand in your browser!

醫療用途

不利影響

化學結構

歷史

成本

參考文獻

外部連結