卡马西平：修订间差异

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我把carbamazepine翻譯為中文，用來補充原來與之連結的卡馬西平的篇幅內容。敬請指教，
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{{medical}}{{Infobox drug
{{medical}}
|verifiedrevid=451682337
|IUPAC_name=5''H''-dibenzo[''b'',''f'']azepine-5-carboxamide
|image=Carbamazepine.svg
|image2=Carbamazepine 3D.png


{{Infobox drug
<!--临床数据-->
| verifiedrevid=451682337
| tradename = 得理多（Tegretol）
| image=Carbamazepine.svg
| Drugs.com = {{drugs.com|药品信息|carbamazepine}}
| width = 175
| DailyMedID = 8d409411-aa9f-4f3a-a52c-fbcb0c3ec053
| alt =
| image2=Carbamazepine-from-xtal-3D-bs-17.png
| width2 = 175
| alt2 =

<!--Clinical data-->
| tradename = Tegretol及其他others
| Drugs.com = {{drugs.com|monograph|carbamazepine}}
| MedlinePlus = a682237
| MedlinePlus = a682237
| DailyMedID = Carbamazepine
| pregnancy_AU = D
| pregnancy_AU = D
| routes_of_administration = [[口服給藥]]
| pregnancy_US = D
| class = {{le|抗癲癇藥|Anticonvulsant}}<ref name=AHFS2015/>
| ATC_prefix=N03
| ATC_suffix=AF01

| legal_AU = S4
| legal_AU = S4
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = Rx-only
| legal_CA = Rx-only
| legal_UK = POM
| legal_UK = POM
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Tegretol FDA label">{{cite web | title=Tegretol- carbamazepine suspension Tegretol- carbamazepine tablet Tegretol XR- carbamazepine tablet, extended release | website=DailyMed | date=16 May 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053 | access-date=2023-01-03}}</ref>
| legal_status = <!-- Rx-only where? -->
| legal_status = <!-- Rx-only where? -->
| routes_of_administration = 口服


<!--药物代谢动力学数据-->
<!--Pharmacokinetic data-->
|bioavailability = ~100%<ref name="carbamazepinelabel"/>
|bioavailability=~100%<ref name = TGA>{{cite web|title=Carbamazepine Drug Label|url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7a1e523a-b377-43dc-b231-7591c4c888ea|accessdate=2016-02-11|archive-date=2014-12-08|archive-url=https://web.archive.org/web/20141208063739/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7a1e523a-b377-43dc-b231-7591c4c888ea|dead-url=no}}</ref>
|protein_bound=70-80%<ref name = TGA/>
|protein_bound = 70–80%<ref name="carbamazepinelabel"/>
|metabolism=[[肝脏]]（[[CYP3A4]]）to active [[环氧化合物|epoxide]] form (carbamazepine-10,11 epoxide)<ref name = TGA/>
|metabolism = [[肝臟]] ([[CYP3A4]])<ref name="carbamazepinelabel"/>
|metabolites = 活性[[環氧化合物]] (carbamazepine-10,11 epoxide)<ref name="carbamazepinelabel"/>
|elimination_half-life=36小时（单次剂量）16-24小时（多次量）<ref name = TGA/>
|elimination_half-life = 36小時 (第一劑), 16–24小時 (後續使用劑量)<ref name="carbamazepinelabel"/>
|excretion=尿液（72%），粪便（28%）<ref name = TGA/>
|excretion = [[尿]]液 (72%)，糞便 (28%)<ref name="carbamazepinelabel"/>


<!--识别信息-->
<!--Identifiers-->
| IUPHAR_ligand = 5339
| IUPHAR_ligand = 5339
|CAS_number_Ref = {{cascite|correct|??}}
|CAS_number_Ref = {{cascite|correct|??}}
|CAS_number=298-46-4
|CAS_number=298-46-4
| CAS_number2 = 85756-57-6
|CAS_supplemental={{CAS|85756-57-6}}
|ATC_prefix=N03
|ATC_suffix=AF01
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI=3387
|ChEBI=3387
第46行： 第56行：
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL=108
|ChEMBL=108
| synonyms = CBZ


<!--化学数据-->
<!--Chemical data-->
| IUPAC_name=5''H''-dibenzo[''b'',''f'']azepine-5-carboxamide
|C=15 |H=12 |N=2 |O=1
|C=15 |H=12 |N=2 |O=1
|molecular_weight=236.269&nbsp;g/mol
|smiles=c1ccc2c(c1)C=Cc3ccccc3N2C(=O)N
|smiles=c1ccc2c(c1)C=Cc3ccccc3N2C(=O)N
|InChI=1/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI=1S/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18)
|StdInChI=1S/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey=FFGPTBGBLSHEPO-UHFFFAOYSA-N}}
|StdInChIKey=FFGPTBGBLSHEPO-UHFFFAOYSA-N
}}

<!-- Definition and uses -->
'''卡马西平'''（{{lang|en|Carbamazepine}}，簡稱'''CBZ'''），商品名'''得理多'''（'''Tegretol'''）是一种治疗[[癫痫病]]和[[神經性疼痛]]的药物<ref name=AHFS2015>{{cite web |title=Carbamazepine |url=http://www.drugs.com/monograph/carbamazepine.html |work=The American Society of Health-System Pharmacists |accessdate=Mar 2015 |archive-url=https://web.archive.org/web/20181203131318/https://www.drugs.com/monograph/carbamazepine.html |archive-date=2018-12-03 |dead-url=yes }}</ref>。同樣能治療癲癇病的還有[[苯妥英]]及[[丙戊酸]]等等<ref>{{cite journal|last=Nolan|first=SJ|author2=Marson, AG |author3=Pulman, J |author4= Tudur Smith, C |title=Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures.|journal=The Cochrane database of systematic reviews|date=23 August 2013|volume=8|pages=CD001769|pmid=23970302|doi=10.1002/14651858.CD001769.pub2}}</ref><ref>{{cite journal|last=Tudur Smith|first=C|author2=Marson, AG |author3=Clough, HE |author4= Williamson, PR |title=Carbamazepine versus phenytoin monotherapy for epilepsy.|journal=The Cochrane database of systematic reviews|year=2002|issue=2|pages=CD001911|pmid=12076427|doi=10.1002/14651858.CD001911}}</ref>，但对{{link-en|失神性發作|absence seizure}}及{{link-en|肌阵挛性发作|Myoclonus}}无用<!-- <ref name=AHFS2015/> -->。本品可與其他藥物併用於治療[[精神分裂症]]，或用於[[躁鬱症]]的二線用藥<ref name=AHFS2015/>，通常一日服用2-4次<ref name=AHFS2015/>。有證據顯示以{{tsl|en|controlled release|改良缓释给药}}有助於減少副作用<ref>{{cite journal|last1=Powell|first1=G|last2=Saunders|first2=M|last3=Marson|first3=AG|title=Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.|journal=The Cochrane database of systematic reviews|date=3 February 2014|volume=2|pages=CD007124|pmid=24488654|doi=10.1002/14651858.CD007124.pub3}}</ref>。
''' 卡馬西平''' （{{lang-en|carbamazepine}}，簡稱CBZ）以Tegretol（得理多）等商品名稱於市面販售，是一種治療[[癲癇]]和[[神經性疼痛]]的{{le|抗癲癇藥|Anticonvulsant}}。<ref name="Tegretol FDA label" /><ref name=AHFS2015>{{cite web|url=https://www.drugs.com/monograph/carbamazepine.html|title=Carbamazepine|work=The American Society of Health-System Pharmacists|access-date=2015-03-28|url-status=live|archive-url=https://web.archive.org/web/20150227213125/http://www.drugs.com/monograph/carbamazepine.html|archive-date= 2015-02-27}}</ref>它可作為輔助藥物，與其他藥物一起治療[[思覺失調]]，並用作治療[[雙相情緒障礙症]]的二線藥物。<ref>{{cite journal | vauthors = Nevitt SJ, Marson AG, Weston J, Tudur Smith C | title = Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | pages = CD001769 | date = August 2018 | issue = 8 | pmid = 30091458 | pmc = 6513104 | doi = 10.1002/14651858.CD001769.pub4 }}</ref><ref name=AHFS2015/>卡馬西平對於局部性和全身性[[癲癇發作]]的作用似乎與[[苯妥英]]和[[丙戊酸]]一樣有效。<ref name=":0">{{cite journal | vauthors = Nevitt SJ, Marson AG, Tudur Smith C | title = Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD001911 | date = July 2019 | issue = 7 | pmid = 31318037 | pmc = 6637502 | doi = 10.1002/14651858.CD001911.pub4 }}</ref>它對於{{le|失神癲癇發作|Absence seizure}}或[[肌陣攣]]發作無治療效果。<ref name=AHFS2015/>

卡馬西平於1953年由[[瑞士]]化學家Walter Schindler發現。<ref>{{cite book| vauthors = Smith HS |title=Current therapy in pain|date=2009|publisher=Saunders/Elsevier|location=Philadelphia|isbn=978-1-4160-4836-7 |page=460|url=https://books.google.com/books?id=iTgy62MWnK4C&pg=PA460|url-status=live|archive-url=https://web.archive.org/web/20160305032812/https://books.google.ca/books?id=iTgy62MWnK4C&pg=PA460|archive-date=5 March 2016}}</ref><ref>{{cite patent |country=US |number=2948718 |status=patent |title=New n-heterocyclic compounds |pubdate=1960-08-09 |gdate=1960-08-09 |fdate=1958-11-20 |pridate=1957-12-20 |invent1=Walter Schindler |assign1=Geigy Chemical Corporation |url=https://worldwide.espacenet.com/patent/search/family/003449474/publication/US2948718A?q=US2948718A}}</ref>於1962年首次被核准在瑞士用於治療癲癇。<ref>{{cite book| vauthors = Moshé S |title=The treatment of epilepsy |date=2009 |publisher=Wiley-Blackwell |location=Chichester, UK |isbn=978-1-4443-1667-4 |page=xxix |edition=3 |url=https://books.google.com/books?id=rFFzFzZJtasC&pg=PR29 |url-status=live|archive-url= https://web.archive.org/web/20160305024852/https://books.google.ca/books?id=rFFzFzZJtasC&pg=PR29 |archive-date=2016-03-05 }}</ref>

==醫療用途==
[[File:Tegretol.jpg|thumb|冠有Tegretol品牌的卡馬西平200毫克控釋[[片劑]]（[[紐西蘭]]製造）。]]

卡馬西平通常用於治療癲癇和神經性疼痛，<ref name=AHFS2015/>也作為治療雙相情緒障礙症的二線藥物（[[仿單標示外使用]]），並在某些思覺失調病例的治療中，當單獨用傳統[[抗精神病藥]]治療失敗時，可作為輔助用藥使用。<ref name=AHFS2015/><ref name="Ceron-Litvoc">{{cite journal | vauthors = Ceron-Litvoc D, Soares BG, Geddes J, Litvoc J, de Lima MS | title = Comparison of carbamazepine and lithium in treatment of bipolar disorder: a systematic review of randomized controlled trials | journal = Human Psychopharmacology | volume = 24 | issue = 1 | pages = 19–28 | date = January 2009 | pmid = 19053079 | doi = 10.1002/hup.990 | s2cid = 5684931 }}</ref>然而證據並不支持將此藥物用於治療思覺失調。<ref>{{cite journal | vauthors = Leucht S, Helfer B, Dold M, Kissling W, McGrath J | title = Carbamazepine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD001258 | date = May 2014 | volume = 2014 | pmid = 24789267 | pmc = 7032545 | doi = 10.1002/14651858.CD001258.pub3 | collaboration = Cochrane Schizophrenia Group }}</ref>它對失神癲癇發作或肌陣攣的治療無效。<ref name=AHFS2015/>雖然卡馬西平可能與苯妥英和丙戊酸具有相似作用和功效，但在藥物選擇上應根據個人情況進行評估，再進一步確定哪種藥物對新發癲癇患者最有幫助。<ref name=":0" />

卡馬西平在美國被註冊為適於治療癲癇（包括{{le|局部性癲癇發作|Focal seizure}}、[[强直-阵挛性发作|全身性強直陣攣發作]]和混合性癲癇發作）及[[三叉神經痛]]。<ref name="Tegretol FDA label" /><ref name="Lexi-Comp"/>卡馬西平是唯一經[[美國食品藥物管理局]]（FDA）核准用於治療三叉神經痛的藥物。<ref>{{Cite journal| vauthors = Pino MA |date= 2017-01-19 |title= Trigeminal Neuralgia: A "Lightning Bolt" of Pain|url=https://www.uspharmacist.com/article/trigeminal-neuralgia-a-lightning-bolt-of-pain|journal=US Pharmacist|volume=42|pages=41–44}}</ref>

截至2014年，市面上有{{le|改良釋放劑量|Modified-release dosage}}製劑販售，初步證據顯示其副作用較少，但療效是否與其他製劑有異，證據尚不明確。<ref>{{cite journal | vauthors = Powell G, Saunders M, Rigby A, Marson AG | title = Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD007124 | date = December 2016 | issue = 4 | pmid = 27933615 | pmc = 6463840 | doi = 10.1002/14651858.CD007124.pub5 }}</ref>

==不良影響==
於美國販售的卡馬西平，包裝的標籤上含有下列警告：<ref name="Tegretol FDA label" />

*對人體產生[[紅血球]]、[[白血球]]和[[血小板]]的影響：發生[[再生不良性貧血]]和{{le|粒細胞減少症|agranulocytosis}}重大影響的報告屬於罕見，常見的是如白血球或血小板數量減少，但不會發展成為更嚴重的問題。<ref name="carbamazepinelabel">{{cite web|title=Carbamazepine Drug Label|url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7a1e523a-b377-43dc-b231-7591c4c888ea|url-status=live|archive-url=https://web.archive.org/web/20141208063739/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7a1e523a-b377-43dc-b231-7591c4c888ea|archive-date=2014-12-08}}</ref>
*[[自殺]]風險升高<ref name=stats>{{cite journal | vauthors = Vukovic Cvetkovic V, Jensen RH | title = Neurostimulation for the treatment of chronic migraine and cluster headache | journal = Acta Neurologica Scandinavica | volume = 139 | issue = 1 | pages = 4–17 | date = January 2019 | pmid = 30291633 | doi = 10.1111/ane.13034 | s2cid = 52923061 | doi-access = free }}</ref>
*[[低鈉血症]]和{{le|不適切抗利尿激素分泌症候群|syndrome of inappropriate antidiuretic hormone secretion}}（SIADH）的風險會增加<ref name="carbamazepinelabel"/><ref>{{cite journal | vauthors = Gandelman MS | s2cid = 36758508 | title = Review of carbamazepine-induced hyponatremia | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 18 | issue = 2 | pages = 211–33 | date = March 1994 | pmid = 8208974 | doi = 10.1016/0278-5846(94)90055-8 }}</ref>
*患者突然停止用藥後，有癲癇發作的風險<ref name="carbamazepinelabel"/>
*[[姙娠|懷孕]]婦女使用後，會對胎兒造成風險，特別是有可能出現[[脊柱裂]]等先天畸形和發育障礙。<ref name="carbamazepinelabel"/><ref>{{cite journal | vauthors = Jentink J, Dolk H, Loane MA, Morris JK, Wellesley D, Garne E, de Jong-van den Berg L | title = Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study | journal = BMJ | volume = 341 | pages = c6581 | date = December 2010 | pmid = 21127116 | pmc = 2996546 | doi = 10.1136/bmj.c6581 }}</ref>
*[[胰腺炎]]
*[[肝炎]]
*[[頭暈]]
*[[骨髓抑制]]
*[[史蒂芬斯－強森症候群]]

常見的不良反應可能有嗜睡、頭暈、[[頭痛]]和[[偏頭痛]]、[[共濟失調]]、[[噁心]]、[[嘔吐]]和/或[[便秘]]。服用卡馬西平期間飲酒，可能會導致[[中樞神經系統]]抑制加劇。<ref name="carbamazepinelabel"/>

較不常見的副作用可能包括混合癲癇症患者癲癇發作風險增加、<ref>{{cite journal | vauthors = Liu L, Zheng T, Morris MJ, Wallengren C, Clarke AL, Reid CA, Petrou S, O'Brien TJ | s2cid = 7693614 | display-authors = 6 | title = The mechanism of carbamazepine aggravation of absence seizures | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 319 | issue = 2 | pages = 790–8 | date = November 2006 | pmid = 16895979 | doi = 10.1124/jpet.106.104968 }}</ref>[[心律不整]]、視力模糊或[[複視]]。<ref name="carbamazepinelabel"/>此外也有罕見聽覺副作用的病例報告，患者感知到的聲音比以前低大約[[半音]]，通常大多數人不會注意到這種不尋常的副作用，且在停止服藥後就會消失。<ref>{{cite journal | vauthors = Tateno A, Sawada K, Takahashi I, Hujiwara Y | title = Carbamazepine-induced transient auditory pitch-perception deficit | journal = Pediatric Neurology | volume = 35 | issue = 2 | pages = 131–4 | date = August 2006 | pmid = 16876011 | doi = 10.1016/j.pediatrneurol.2006.01.011 }}</ref>

===藥物基因學===
使用卡馬西平而導致的嚴重皮膚反應，如史蒂芬斯－強森症候群（SJS）或{{le|中毒性表皮壞死鬆解症|toxic epidermal necrolysis }}（TEN），在攜帶特定[[人類白血球抗原]]基因變異（[[等位基因]]）{{le|HLA-B *1502|HLA-B75 }}的人群中較為常見。<ref name="carbamazepinelabel"/>攜帶等位基因的人發生SJS或TEN的{{le|發生比|Odd ratio}}有可能達到兩位數（10的倍數）、三位數（百的倍數）甚至是四位數（千的倍數），取決於所屬的族群。<ref>{{cite journal | vauthors = Kaniwa N, Saito Y | title = Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury | journal = Journal of Human Genetics | volume = 58 | issue = 6 | pages = 317–26 | date = June 2013 | pmid = 23635947 | doi = 10.1038/jhg.2013.37 | doi-access = free }}</ref><ref name="pmid24597466">{{cite journal | vauthors = Amstutz U, Shear NH, Rieder MJ, Hwang S, Fung V, Nakamura H, Connolly MB, Ito S, Carleton BC | display-authors = 6 | title = Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions | journal = Epilepsia | volume = 55 | issue = 4 | pages = 496–506 | date = April 2014 | pmid = 24597466 | doi = 10.1111/epi.12564 | hdl = 2429/63109 | s2cid = 41565230 | hdl-access = free }}</ref>HLA-B*1502幾乎只出現在廣大地區的[[亞洲]]血統人群中，但在[[歐洲]]、[[日本]]、[[韓國]]和[[非洲]人群中出現的頻率非常低，或是不存在。<ref name="carbamazepinelabel"/><ref>{{cite journal | vauthors = Leckband SG, Kelsoe JR, Dunnenberger HM, George AL, Tran E, Berger R, Müller DJ, Whirl-Carrillo M, Caudle KE, Pirmohamed M | display-authors = 6 | title = Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 3 | pages = 324–8 | date = September 2013 | pmid = 23695185 | pmc = 3748365 | doi = 10.1038/clpt.2013.103 }}</ref>然而攜帶有HLA-A*31:01等位基因的人群（如日本、[[中國]]、韓國和歐洲人）已成為會明顯受到卡馬西平導致的輕度和嚴重不良反應（例如{{le|藥物疹合併嗜伊紅血症及全身症狀|Drug rash with eosinophilia and systemic symptoms}}（DRESS）形式的嚴重皮膚反應）的族群。<ref name="pmid24597466"/><ref name="pmid28345177">{{cite journal | vauthors = Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA, Phillips EJ | title = Pharmacogenomics of off-target adverse drug reactions | journal = British Journal of Clinical Pharmacology | volume = 83 | issue = 9 | pages = 1896–1911 | date = September 2017 | pmid = 28345177 | pmc = 5555876 | doi = 10.1111/bcp.13294 }}</ref>研究顯示卡馬西平為一種有效抗原，可與HLA-B*1502類似的抗原呈現區域結合，在未成熟的[[細胞毒性T細胞]]上觸發持久的激活信號，而導致廣泛的細胞毒性反應，如前述的SJS及TEN。<ref>{{cite journal | vauthors = Jaruthamsophon K, Tipmanee V, Sangiemchoey A, Sukasem C, Limprasert P | title = HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 45553 | date = March 2017 | pmid = 28358139 | pmc = 5372085 | doi = 10.1038/srep45553 | bibcode = 2017NatSR...745553J }}</ref>

==交互作用==
卡馬西平具有潛在的[[藥物相互作用]]。<ref name="Lexi-Comp">{{cite web|url=http://www.merck.com/mmpe/lexicomp/carbamazepine.html |title=Carbamazepine |date=February 2009 |author=Lexi-Comp |work=[[Merck Manual of Diagnosis and Therapy|The Merck Manual Professional]] |archive-url=https://web.archive.org/web/20101103035532/http://www.merck.com/mmpe/lexicomp/carbamazepine.html |archive-date=2010-11-03 |url-status=live }} Retrieved on 2009-05-03.</ref>可降低卡馬西平分解或以其他方式增加其水平的藥物有[[紅黴素]]、<ref name=Stafstrom>{{cite journal | vauthors = Stafstrom CE, Nohria V, Loganbill H, Nahouraii R, Boustany RM, DeLong GR | title = Erythromycin-induced carbamazepine toxicity: a continuing problem | journal = Archives of Pediatrics & Adolescent Medicine | volume = 149 | issue = 1 | pages = 99–101 | date = January 1995 | pmid = 7827672 | doi = 10.1001/archpedi.1995.02170130101025 | url = http://archpedi.ama-assn.org/cgi/pmidlookup?view=long&pmid=7827672 | url-status = live | archive-url = https://www.webcitation.org/5uKvQB98w?url=http://archpedi.ama-assn.org/cgi/pmidlookup?view=long&pmid=7827672 | archive-date = 2010-11-18 }}</ref>[[西咪替丁]]、{{le|右旋丙氧芬|Dextropropoxyphene}}和[[鈣通道阻滯劑]]。<ref name="Lexi-Comp"/>[[葡萄柚]]汁會抑制腸壁和肝臟中的[[CYP3A4]]酵素而提高卡馬西平的[[生物利用度]]。<ref name="carbamazepinelabel"/>當此藥物與苯巴比妥、苯妥英或{{le|撲米酮|primidone}}一起使用時，會將卡馬西平的水平降低，而可能導致突破性癲癇發作。<ref name="urleMedicine- Toxicity, Carbamazepine" />

丙戊酸和{{le|伐諾拉酰胺|valnoctamide}}會抑制{{le|微粒體環氧化物水解酶|microsomal epoxide hydrolase}} (mEH)，而mEH負責將卡馬西平活性代謝物 - 卡馬西平-10,11-環氧化物 - 分解為無活性代謝物。<ref>{{cite book | vauthors = Gonzalez FJ, Tukey RH | veditors = Brunton L, Lazo J, Parker K |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics |edition=11th |year=2006 |publisher=[[McGraw-Hill]] |location=New York |isbn=978-0-07-142280-2 |page=[https://archive.org/details/goodmangilmansph00brun_116/page/n104 79] |chapter=Drug Metabolism|title-link=Goodman & Gilman's The Pharmacological Basis of Therapeutics }}</ref>丙戊酸和伐諾拉酰胺因抑制mEH而引起活性代謝物積累，會延長卡馬西平的作用並延遲其被人體排泄。

卡馬西平是[[細胞色素P450]]酶的誘導劑，可能會增加許多藥物的清除率，將藥物在血液中的濃度降低至亞治療水平，並將預期效果降低。<ref name="urleMedicine- Toxicity, Carbamazepine">{{cite web |url= http://www.emedicine.com/emerg/topic77.htm | work = eMedicine | title = Carbamazepine Toxicity |archive-url=https://web.archive.org/web/20080704144842/http://emedicine.com/emerg/topic77.htm |archive-date=2008-07-04 |url-status=live |date=2 February 2019 }}</ref>卡馬西平會加快以下藥物的代謝：[[華法林]]、[[拉莫三嗪]]、苯妥英、[[茶鹼]]、丙戊酸、<ref name="Lexi-Comp"/>多種[[苯二氮平類]]藥物<ref name="isbn1-58829-211-8">{{cite book | vauthors = Moody D | veditors = Raymon LP, Mozayani A |title=Handbook of Drug Interactions: a Clinical and Forensic Guide |publisher=Humana |year=2004 |pages=[https://archive.org/details/handbookofdrugin0000unse/page/3 3–88] |chapter=Drug interactions with benzodiazepines |isbn=978-1-58829-211-7 |chapter-url-access=registration |chapter-url=https://archive.org/details/handbookofdrugin0000unse/page/3 }}</ref>和[[美沙酮]]。<ref>{{cite journal | vauthors = Schlatter J, Madras JL, Saulnier JL, Poujade F | title = [Drug interactions with methadone] | language = fr | journal = Presse Médicale | volume = 28 | issue = 25 | pages = 1381–4 | date = September 1999 | pmid = 10506872 | trans-title = Drug interactions with methadone }}</ref>卡馬西平也會增加[[避孕藥]]中[[激素]]的代謝，可能降低其有效性而導致意料之外的受孕發生。<ref name="Lexi-Comp"/>

==藥理學==
===作用機轉===
卡馬西平是一種[[鈉離子通道阻滯劑]]。<ref>{{cite journal | vauthors = Rogawski MA, Löscher W, Rho JM | title = Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet | journal = Cold Spring Harbor Perspectives in Medicine | volume = 6 | issue = 5 | pages = a022780 | date = 2016-05-02 | pmid = 26801895 | pmc = 4852797 | doi = 10.1101/cshperspect.a022780 }}</ref>它優先結合處於非活性構象的電壓門控[[鈉離子通道]]，而防止[[動作電位]]的重複和持續放電。卡馬西平對血清素系統有影響，但與抗癲癇作用的相關性尚不確定。有證據顯示它是一種{{le|血清素釋放劑|serotonin releasing agent}}，甚至可能是一種{{le|血清素再攝取抑制劑|serotonin reuptake inhibitor}}。<ref>{{cite journal | vauthors = Dailey JW, Reith ME, Steidley KR, Milbrandt JC, Jobe PC | title = Carbamazepine-induced release of serotonin from rat hippocampus in vitro | journal = Epilepsia | volume = 39 | issue = 10 | pages = 1054–63 | date = October 1998 | pmid = 9776325 | doi = 10.1111/j.1528-1157.1998.tb01290.x | s2cid = 20382623 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dailey JW, Reith ME, Yan QS, Li MY, Jobe PC | title = Carbamazepine increases extracellular serotonin concentration: lack of antagonism by tetrodotoxin or zero Ca2+ | journal = European Journal of Pharmacology | volume = 328 | issue = 2–3 | pages = 153–62 | date = June 1997 | pmid = 9218697 | doi = 10.1016/s0014-2999(97)83041-5 }}</ref><ref>{{cite journal | vauthors = Kawata Y, Okada M, Murakami T, Kamata A, Zhu G, Kaneko S | title = Pharmacological discrimination between effects of carbamazepine on hippocampal basal, Ca(2+)- and K(+)-evoked serotonin release | journal = British Journal of Pharmacology | volume = 133 | issue = 4 | pages = 557–67 | date = June 2001 | pmid = 11399673 | pmc = 1572811 | doi = 10.1038/sj.bjp.0704104 }}</ref>有人認為卡馬西平還可阻斷電壓門控鈣通道，而減少神經傳導物質釋放。<ref>{{cite journal | vauthors = Gambeta E, Chichorro JG, Zamponi GW | title = Trigeminal Neuralgia: an overview from pathophysiology to pharmacological treatments | journal = Molecular Pain |date = January 2020 | volume = 16 | pmid = 31908187| doi = 10.1177/1744806920901890 | pmc = 6985973 }}</ref>

===藥物動力學===
[[File:Carbamazepine metabolism.svg|thumb|upright=0.7|卡馬西平代謝過程：上：卡馬西平•中：卡馬西平-10,11-環氧化物（活化代謝物）•下：卡馬西平-反式-10,11-二醇（滅活代謝物），之後成為葡萄醣醛酸苷。]]

卡馬西平經口服後，人體吸收速度相對緩慢但幾乎可完全吸收。根據劑型，4至24小時後其於血漿中濃度會達到峰值。緩釋片劑的吸收率會比一般[[片劑]]的降低約15%，血漿峰值濃度降低約25%，且濃度波動較小，但[[最小血藥濃度]]並未顯著降低。<ref name="PubChem">{{cite web |title=Carbamazepine |url= https://pubchem.ncbi.nlm.nih.gov/compound/2554 |access-date=6 May 2021|work = PubChem | publisher = National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services }}</ref><ref name="AC">{{cite book|title=Austria-Codex| veditors = Haberfeld H |at=Tegretol retard 400 mg-Filmtabletten|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2021|language=German}}</ref>


在血液循環中，卡馬西平本身佔總殘留量的20%至30%，其餘的是代謝物，70%至80%的殘留物與血漿蛋白結合。母乳中的濃度是血漿中濃度的25%至60%。<ref name="AC" />
<!-- Side effects -->
常見副作用包含[[恶心]]和[[drowsiness|昏睡]]<!-- <ref name=AHFS2015/> -->。可能發生的嚴重副作用則包含皮膚紅疹[[骨髓]]功能下降、{{tsl|en|suicidal thoughts||自殺衝動}}，或意識渾沌<!-- <ref name=AHFS2015/> -->。有骨髓疾病或歷史者不可服用<!-- <ref name=AHFS2015/> -->。[[妊娠]]期間用藥可能會對胎兒造成傷害，但若孕婦本身患有癲癇，則不建議在妊娠期間貿然停藥<!-- <ref name=AHFS2015/> -->。[[母乳餵養|哺乳]]期間不建議服藥<!-- <ref name=AHFS2015/> -->。有肝腎問題者如服用此藥須額外關注<ref name=AHFS2015/>。


卡馬西平本身不具有藥理活性。它主要被CYP3A4激活，並生成卡馬西平-10,11-環氧化物，此環氧化物是抗癲癇作用的唯一來源。然後環氧化物被微粒體環氧化物水解酶 (mEH) 滅活，生成卡馬西平-反式-10,11-二醇，進一步再成為{{le|葡萄醣醛酸苷|glucuronide}}。其他代謝物有各種[[羥基]]衍生物和卡馬西平-N-葡萄醣醛酸苷。<ref name="AC" />
<!-- Society, culture and history -->
卡马西平最早於1953年由瑞士化學家[[瓦特·辛德勒]]（Walter Schindler）所發現<ref>{{cite book|last1=Smith|first1=Howard S.|title=Current therapy in pain|date=2009|publisher=Saunders/Elsevier|location=Philadelphia|isbn=9781416048367|page=460|url=https://books.google.ca/books?id=iTgy62MWnK4C&pg=PA460|access-date=2016-05-11|archive-date=2016-03-05|archive-url=https://web.archive.org/web/20160305032812/https://books.google.ca/books?id=iTgy62MWnK4C&pg=PA460|dead-url=no}}</ref>，並於1962年首次上市<ref>{{cite book|last1=Moshé|first1=Solomon|title=The treatment of epilepsy|date=2009|publisher=Wiley-Blackwell|location=Chichester, UK|isbn=9781444316674|page=xxix|edition=3|url=https://books.google.ca/books?id=rFFzFzZJtasC&pg=PR29|access-date=2016-05-11|archive-date=2016-03-05|archive-url=https://web.archive.org/web/20160305024852/https://books.google.ca/books?id=rFFzFzZJtasC&pg=PR29|dead-url=no}}</ref>。該藥目前屬於[[通用名药物|學名藥]]，價格低廉<ref>{{cite book|title=Principles and practice of stereotactic radiosurgery|date=2008|publisher=Springer|location=New York|isbn=9780387710709|page=536|url=https://books.google.ca/books?id=uEghr21XY6wC&pg=PA536|access-date=2016-05-11|archive-date=2016-03-05|archive-url=https://web.archive.org/web/20160305021147/https://books.google.ca/books?id=uEghr21XY6wC&pg=PA536|dead-url=no}}</ref>。該藥列名[[世界卫生组织基本药物标准清单]]之中，為基礎公衛體系必備藥物之一<ref>{{cite web|title=WHO Model List of Essential Medicines|format=PDF|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013|archive-date=2014-04-23|archive-url=https://web.archive.org/web/20140423005004/http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|dead-url=no}}</ref>。在2014年，本品的批發價位於每劑0.01至0.07[[美元]]之間<ref>{{cite web|title=Carbamazepine|url=http://erc.msh.org/dmpguide/resultsdetail.cfm?language=english&code=CBM200T&s_year=2014&year=2014&str=200%20mg&desc=Carbamazepine&pack=new&frm=TAB-CAP&rte=PO&class_code2=24%2E2%2E&supplement=&class_name=%2805%2E%29Anticonvulsants%2Fantiepileptics%3Cbr%3E%2824%2E2%2E%29Medicines%20used%20in%20mood%20disorders%3Cbr%3E|website=International Drug Price Indicator Guide|accessdate=2 December 2015}}{{dead link|date=2018年5月 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>。


卡馬西平單次劑量給藥的[[生物半衰期]]約為35～40小時，但它是細胞色素P450酶的強誘導劑，重複給藥時的生物半衰期縮短至約12～17小時。其他酵素誘導劑如苯妥英或苯巴比妥可將半衰期進一步縮短至9-10小時。此藥物約有70%會經由[[尿]]液排出（幾乎全為代謝物形式），30%經由糞便排出。<ref name="PubChem" /><ref name="AC" />
== 作用和細節 ==
=== 適應症 ===
* 精[[運動]]性[[癲癇]]發作（單獨使用，或與primidone或[[苯妥英]]（phenytoin）一起使用）
* [[癲癇]]大發作（與phenytoin併用）
* 混合型的[[癲癇]]發作
* 緩解與三叉神經痛有關的疼痛
* 躁症和[[躁郁症]]的預防
* [[酒精]]禁戒症候群
* 腎原性[[糖尿病]]崩症
* [[糖尿病]]性神經病變之疼痛
* [[癲癇]]性格及附隨癲癇之精神障礙
* 尿崩症


==歷史==
=== 藥動力學 ===
卡馬西平是1953年由在J.R. Geigy AG（後被藥業[[諾華]]併入）工作的瑞士化學家Walter Schindler所發現。<ref name=Scott1993>{{cite book | vauthors = Scott DF | chapter = Chapter 8: Carbamazepine | title = The History of Epileptic Therapy: An Account of How Medication was Developed. | series = History of Medicine Series. | publisher = CRC Press | date = 1993 | isbn = 978-1-85070-391-4 }}</ref><ref>{{cite journal |vauthors=Schindler W, Häfliger F |title=Über Derivate des Iminodibenzyls |journal=[[Helvetica Chimica Acta]] |year=1954 |volume=37 |issue=2 |pages=472–83 |doi=10.1002/hlca.19540370211}}</ref>其於1963年首次作為治療癲癇的藥物在瑞士上市，商品名為Tegretol，同時又用於治療三叉神經痛。<ref name=Scott1993/>英國自1965年起用其作抗癲癇藥，美國於1968年批准其用作醫療用途。<ref name=AHFS2015/>
* 口服吸收緩慢，但是完全[[血漿]]尖峰濃度在2～6小時出現，在體內廣泛分佈，與[[蛋白質]]有高度的結合，血清[[半衰期]]約15～30小時，它在[[肝臟]]中代謝（其[[過氧化物]]的代謝物具有抗驚厥的活性），以好幾種代謝物和某部份未改變的[[藥物]]經由[[腎臟]]排出體外。


此藥物在20世紀70年代一直被研究用於治療雙相情緒障礙症。<ref name="pmid9682927">{{cite journal | vauthors = Okuma T, Kishimoto A | title = A history of investigation on the mood stabilizing effect of carbamazepine in Japan | journal = Psychiatry and Clinical Neurosciences | volume = 52 | issue = 1 | pages = 3–12 | date = February 1998 | pmid = 9682927 | doi = 10.1111/j.1440-1819.1998.tb00966.x | s2cid = 8480811 }}</ref>
=== 交互作用 ===
* 通常並不推薦同時使用卡马西平與 MAO 抑制劑或三環類抗抑鬱劑，因為毒性會增加。
* 卡马西平具有很高的[[蛋白]][[結合率]]，因此，它會將其他[[蛋白]]結合的[[藥物]]（如水杨酸盐（salicylates）、口服降[[血糖]]藥、抗凝血劑、抗[[發炎]]劑）從蛋白結合的位置取代出來，而加強它們的藥效。
* 克拉霉素（Clarithromycin）、红霉素（Erythromycin）、 醋竹桃霉素（Troleandomycin）會抑制卡马西平的[[肝臟]]代謝，而增強其[[藥理]]與毒性作用。處理：避免。
* 特非那定（Terfenadine）會提昇卡马西平的血中濃度和不良反應。處理：監測。
* Carbamazepine是少見自我誘導(self-induced)藥物，因為在藥物代謝酵素P450中Carbamazepine同時是CYP3A4的受質(substract)也是誘導劑(inducer)，因此Carbamazepine的在血液中的半衰期會越來越短。


目前市面已有此藥物的[[通用名藥物]]流通。<ref>{{cite book | vauthors = Porter NC | chapter = Trigeminal Neuralgia: Surgical Perspective | veditors = Chin LS, Regine WF |title=Principles and practice of stereotactic radiosurgery |date=2008 |publisher=Springer |location=New York |isbn=978-0-387-71070-9 | chapter-url= https://books.google.com/books?id=uEghr21XY6wC&pg=PA536 |url-status=live |archive-url= https://web.archive.org/web/20160305021147/https://books.google.ca/books?id=uEghr21XY6wC&pg=PA536 |archive-date=2016-03-05 | page = 536 }}</ref>卡馬西平已被列入[[世界衛生組織基本藥物標準清單]]之中。<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = [[World Health Organization]] | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free | last1 = Organization | first1 = World Health }}</ref>此藥物於2020年在美國最常用[[處方藥]]中排名第185，開立的處方箋超過200萬張。<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 2022-10-07}}</ref><ref>{{cite web | title = Carbamazepine - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Carbamazepine | access-date =2022-10-07}}</ref>
=== 藥理作用 ===
* 增加[[潛伏期]]，減少反應性，抑制放電後與皮質和邊緣功能有關的多突觸途徑
* 可降低強直後藥力相乘的作用，此外，它還具有抗膽鹼激性，抗抑鬱和[[肌肉]]鬆弛的作用（干擾經[[肌肉]]的傳遞作用）
* 可以預防大部份特發性三叉神經痛患者的陣發性疼痛
* 在[[酒精]]脫癮症候群方面，可提高已被降低的驚厥閾值，因而減少病症突發的危險性
* 它並可迅速地改善精神性與自主神經性神經不安的症狀
* 在尿崩症方面，本品可以迅速減低尿量，解除乾渴感


== 注意事項 ==
==社會與文化==
===環境影響===
* 罹患腎、肝或[[心臟]]疾病、[[高血壓]]、[[青光眼]]的患者，以及老人、孕婦或授乳的病人等使用宜小心；
{{main|藥物與個人護理用品對環境的影響}}
* 停藥要慢慢的調整劑量，若突然的改變，可能會導致[[癲癇重積狀態]]；
* 卡马西平須在監測下小心使用。服用本品不宜開車或從事危險性工作；
* 有嚴重心血管方面的[[疾病]]，或者肝腎功能異常及老年人，使用卡马西平須注意調整劑量；
* [[骨髓]]抑制的病歷，和嚴重的[[高血壓]]、對卡马西平過敏者，[[心臟]]房室阻斷的病人，不可服用。


在美國污水處理廠的污水中<ref name="Prosser">{{cite journal | vauthors = Prosser RS, Sibley PK | title = Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation | journal = Environment International | volume = 75 | pages = 223–33 | date = February 2015 | pmid = 25486094 | doi = 10.1016/j.envint.2014.11.020 }}</ref>{{rp|224}} 以及接受污水處理廠排出水的溪流中可檢測出卡馬西平及其生物轉化產物的蹤跡。<ref name="pmid30350841">{{cite journal | vauthors = Posselt M, Jaeger A, Schaper JL, Radke M, Benskin JP | title = Determination of polar organic micropollutants in surface and pore water by high-resolution sampling-direct injection-ultra high performance liquid chromatography-tandem mass spectrometry | journal = Environmental Science: Processes & Impacts | volume = 20 | issue = 12 | pages = 1716–1727 | date = December 2018 | pmid = 30350841 | doi = 10.1039/C8EM00390D | doi-access = free }}</ref>相關機構已進行過現場和實驗室研究，以了解在摻有來自污水處理廠污泥的土壤中所生長的食品植物中此藥物的積累情況，及其隨著污泥中存在的藥物濃度和土壤中污泥成分的變化而變化的後續結果。於2014年所發表的一項審查，結論是"根據該研究結果，在用含有卡馬西平的生物固體所改良的土壤中生長的植物，其積累程度對人類健康構成微不足道的風險。"<ref name=Prosser/>{{rp|227}}
== 常見副作用 ==
# 严重、有时致命的皮肤反应，包括[[中毒性表皮坏死松解症]]和[[史蒂芬斯-強森症候群|史蒂文斯-约翰逊综合征]]（Stevens-Johnson syndrome）在卡马西平-{}-治疗中报告。研究发现此反应的风险和[[HLA-B基因]]的继承变种[[HLA-B*1502]]的存在有关联。<ref>[http://www.fda.gov/bbs/topics/NEWS/2007/NEW01755.html Carbamazepine Prescribing Information to Include Recommendation of Genetic Test for Patients with Asian Ancestry] {{Wayback|url=http://www.fda.gov/bbs/topics/NEWS/2007/NEW01755.html |date=20090514031420 }}，FDA</ref>
# 食慾減退
# 口乾
# 乾嘔
# [[腹瀉]]或[[便秘]]
# [[頭痛]]
# [[暈眩]]
# [[嗜睡]]
# [[運動]]失調
# 視覺調節作用異常
# 複視
# 老年人偶爾發生的精神上混亂及激動


===品牌名稱===
尤其在治療初期、通常經過7～14天或暫時降低劑量，這些副作用就會自然消失，其他因本品的抗利尿作用導致的低血鈉症，有時無伴隨[[嘔吐]]、[[頭痛]]、精神混亂，則較少發生，[[白血球]]減少症、[[血小板]]減少症、顆粒性[[白血球]]缺乏症、再生不良性[[貧血]]、[[血栓]]性栓塞、[[心臟]]傳導異常、[[肝炎]]、蛋白尿、[[淋巴結]]腫脹等也曾過報告。
卡馬西平在全球以許多品牌出售，Tegretol是其中之一。<ref>{{cite web |title=Carbamazepine |url=https://www.drugs.com/international/carbamazepine.html |website=Drugs.com |access-date= 2019-10-27 |language=en}}</ref>


==註釋==
== 參見 ==
{{reflist|2}}
{{Reflist|2}}


== 参考文献 ==
== 延伸閱讀 ==
{{refbegin}}
{{refbegin}}
* {{cite journal | vauthors = Iqbal MM, Gundlapalli SP, Ryan WG, Ryals T, Passman TE | title = Effects of antimanic mood-stabilizing drugs on fetuses, neonates, and nursing infants | journal = Southern Medical Journal | volume = 94 | issue = 3 | pages = 304–22 | date = March 2001 | pmid = 11284518 | doi = 10.1097/00007611-200194030-00007 | url = https://www.medscape.com/viewarticle/410736_4 }}
* CARBAMAZEPINE [http://www.ktgh.com.tw/Medicament_tbDrug_Look.asp?CatID=124&ModuleType=Y&NewsID=173 光田綜合醫院] {{Wayback|url=http://www.ktgh.com.tw/Medicament_tbDrug_Look.asp?CatID=124&ModuleType=Y&NewsID=173 |date=20190611090947 }}
* {{cite book | title=Medical Genetics Summaries | chapter=Carbamazepine Therapy and HLA Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK321445/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2015 | pmid=28520367 | id=Bookshelf ID: NBK321445 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}
{{refend}}
{{refend}}


==外部連結==
== 外部連結 ==
{{Commons category|Carbamazepine}}
{{Commons category}}
* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/carbamazepine | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Carbamazepine }}
* [https://www.nhs.uk/medicines/carbamazepine/ Carbamazepine]. UK [[National Health Service]]


{{抗癫痫药}}
{{模板:抗癲癇藥}}
{{模板:情緒穩定劑}}
{{通道阻滞剂}}
{{模板:通道阻滯劑}}
{{情绪稳定剂}}
{{模板:GABAA受体正向变构调节剂}}
{{注意力不足过动症的药物治疗}}
{{模板:異生素敏感受體調節劑}}
{{通道阻滞剂}}
{{Neuropathic pain and fibromyalgia pharmacotherapies}}
{{GABAA受体正向变构调节剂}}
{{Tricyclics}}
{{异生素敏感受体调节剂}}
{{Portal bar | Medicine}}
{{Authority control}}


{{draft categories|
[[Category:抗痉挛药物]]
[[分類:抗痙攣藥物]]
[[Category:情绪稳定剂]]
[[分類:二苯並氮䓬]]
[[Category:前药]]
[[Category:脲]]
[[Category:世界卫生组织基本药物]]
[[Category:二苯并氮䓬]]
[[Category:肝毒素]]
[[Category:GABAA受体正向变构调节剂]]
[[Category:GABAA受体正向变构调节剂]]
[[分類:肝毒素]]
[[分類:情緒穩定劑]]
[[分類:前藥]]
[[分類:脲]]
[[分類:世界衛生組織基本藥物]]
[[分類:RTT]]
[[Category:Antidiuretics]]
[[Category:CYP3A4 inducers]]
[[Category:Dermatoxins]]
[[Category:Drugs developed by Novartis]]
}}

2024年4月14日 (日) 15:22的版本

维基百科中的醫學内容仅供参考，並不能視作專業意見。如需獲取醫療幫助或意見，请咨询专业人士。詳見醫學聲明。
卡马西平
臨床資料
商品名（英语：Drug nomenclature）Tegretol及其他others
其他名稱CBZ
AHFS/Drugs.comMonograph
MedlinePlusa682237
核准狀況
懷孕分級
  • 澳: D
给药途径口服給藥
藥物類別（英语：Drug class）抗癲癇藥（英语：Anticonvulsant）[1]
ATC碼
法律規範狀態
法律規範
藥物動力學數據
生物利用度~100%[3]
血漿蛋白結合率70–80%[3]
药物代谢肝臟 (CYP3A4)[3]
代謝產物活性環氧化合物 (carbamazepine-10,11 epoxide)[3]
生物半衰期36小時 (第一劑), 16–24小時 (後續使用劑量)[3]
排泄途徑尿液 (72%)，糞便 (28%)[3]
识别信息
  • 5H-dibenzo[b,f]azepine-5-carboxamide
CAS号298-46-4（85756-57-6）  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)
ECHA InfoCard100.005.512 編輯維基數據鏈接
化学信息
化学式C15H12N2O
摩尔质量236.27 g·mol−1
3D模型（JSmol（英语：JSmol））
  • c1ccc2c(c1)C=Cc3ccccc3N2C(=O)N
  • InChI=1S/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18) checkY
  • Key:FFGPTBGBLSHEPO-UHFFFAOYSA-N checkY

卡馬西平 （英語：carbamazepine，簡稱CBZ）以Tegretol（得理多）等商品名稱於市面販售，是一種治療癲癇和神經性疼痛的抗癲癇藥（英语：Anticonvulsant）。[2][1]它可作為輔助藥物，與其他藥物一起治療思覺失調，並用作治療雙相情緒障礙症的二線藥物。[5][1]卡馬西平對於局部性和全身性癲癇發作的作用似乎與苯妥英和丙戊酸一樣有效。[6]它對於失神癲癇發作（英语：Absence seizure）或肌陣攣發作無治療效果。[1]

卡馬西平於1953年由瑞士化學家Walter Schindler發現。[7][8]於1962年首次被核准在瑞士用於治療癲癇。[9]

醫療用途

冠有Tegretol品牌的卡馬西平200毫克控釋片劑（紐西蘭製造）。

卡馬西平通常用於治療癲癇和神經性疼痛，[1]也作為治療雙相情緒障礙症的二線藥物（仿單標示外使用），並在某些思覺失調病例的治療中，當單獨用傳統抗精神病藥治療失敗時，可作為輔助用藥使用。[1][10]然而證據並不支持將此藥物用於治療思覺失調。[11]它對失神癲癇發作或肌陣攣的治療無效。[1]雖然卡馬西平可能與苯妥英和丙戊酸具有相似作用和功效，但在藥物選擇上應根據個人情況進行評估，再進一步確定哪種藥物對新發癲癇患者最有幫助。[6]

卡馬西平在美國被註冊為適於治療癲癇（包括局部性癲癇發作（英语：Focal seizure）、全身性強直陣攣發作和混合性癲癇發作）及三叉神經痛。[2][12]卡馬西平是唯一經美國食品藥物管理局（FDA）核准用於治療三叉神經痛的藥物。[13]

截至2014年，市面上有改良釋放劑量（英语：Modified-release dosage）製劑販售，初步證據顯示其副作用較少，但療效是否與其他製劑有異，證據尚不明確。[14]

不良影響

於美國販售的卡馬西平，包裝的標籤上含有下列警告：[2]

常見的不良反應可能有嗜睡、頭暈、頭痛和偏頭痛、共濟失調、噁心、嘔吐和/或便秘。服用卡馬西平期間飲酒，可能會導致中樞神經系統抑制加劇。[3]

較不常見的副作用可能包括混合癲癇症患者癲癇發作風險增加、[18]心律不整、視力模糊或複視。[3]此外也有罕見聽覺副作用的病例報告，患者感知到的聲音比以前低大約半音，通常大多數人不會注意到這種不尋常的副作用，且在停止服藥後就會消失。[19]

藥物基因學

使用卡馬西平而導致的嚴重皮膚反應，如史蒂芬斯－強森症候群（SJS）或中毒性表皮壞死鬆解症（英语：toxic epidermal necrolysis）（TEN），在攜帶特定人類白血球抗原基因變異（等位基因）HLA-B *1502（英语：HLA-B75）的人群中較為常見。[3]攜帶等位基因的人發生SJS或TEN的發生比（英语：Odd ratio）有可能達到兩位數（10的倍數）、三位數（百的倍數）甚至是四位數（千的倍數），取決於所屬的族群。[20][21]HLA-B*1502幾乎只出現在廣大地區的亞洲血統人群中，但在歐洲、日本、韓國和[[非洲]人群中出現的頻率非常低，或是不存在。[3][22]然而攜帶有HLA-A*31:01等位基因的人群（如日本、中國、韓國和歐洲人）已成為會明顯受到卡馬西平導致的輕度和嚴重不良反應（例如藥物疹合併嗜伊紅血症及全身症狀（英语：Drug rash with eosinophilia and systemic symptoms）（DRESS）形式的嚴重皮膚反應）的族群。[21][23]研究顯示卡馬西平為一種有效抗原，可與HLA-B*1502類似的抗原呈現區域結合，在未成熟的細胞毒性T細胞上觸發持久的激活信號，而導致廣泛的細胞毒性反應，如前述的SJS及TEN。[24]

交互作用

卡馬西平具有潛在的藥物相互作用。[12]可降低卡馬西平分解或以其他方式增加其水平的藥物有紅黴素、[25]西咪替丁、右旋丙氧芬（英语：Dextropropoxyphene）和鈣通道阻滯劑。[12]葡萄柚汁會抑制腸壁和肝臟中的CYP3A4酵素而提高卡馬西平的生物利用度。[3]當此藥物與苯巴比妥、苯妥英或撲米酮（英语：primidone）一起使用時，會將卡馬西平的水平降低，而可能導致突破性癲癇發作。[26]

丙戊酸和伐諾拉酰胺（英语：valnoctamide）會抑制微粒體環氧化物水解酶（英语：microsomal epoxide hydrolase） (mEH)，而mEH負責將卡馬西平活性代謝物 - 卡馬西平-10,11-環氧化物 - 分解為無活性代謝物。[27]丙戊酸和伐諾拉酰胺因抑制mEH而引起活性代謝物積累，會延長卡馬西平的作用並延遲其被人體排泄。

卡馬西平是細胞色素P450酶的誘導劑，可能會增加許多藥物的清除率，將藥物在血液中的濃度降低至亞治療水平，並將預期效果降低。[26]卡馬西平會加快以下藥物的代謝：華法林、拉莫三嗪、苯妥英、茶鹼、丙戊酸、[12]多種苯二氮平類藥物[28]和美沙酮。[29]卡馬西平也會增加避孕藥中激素的代謝，可能降低其有效性而導致意料之外的受孕發生。[12]

藥理學

作用機轉

卡馬西平是一種鈉離子通道阻滯劑。[30]它優先結合處於非活性構象的電壓門控鈉離子通道，而防止動作電位的重複和持續放電。卡馬西平對血清素系統有影響，但與抗癲癇作用的相關性尚不確定。有證據顯示它是一種血清素釋放劑（英语：serotonin releasing agent），甚至可能是一種血清素再攝取抑制劑（英语：serotonin reuptake inhibitor）。[31][32][33]有人認為卡馬西平還可阻斷電壓門控鈣通道，而減少神經傳導物質釋放。[34]

藥物動力學

卡馬西平代謝過程：上：卡馬西平•中：卡馬西平-10,11-環氧化物（活化代謝物）•下：卡馬西平-反式-10,11-二醇（滅活代謝物），之後成為葡萄醣醛酸苷。

卡馬西平經口服後，人體吸收速度相對緩慢但幾乎可完全吸收。根據劑型，4至24小時後其於血漿中濃度會達到峰值。緩釋片劑的吸收率會比一般片劑的降低約15%，血漿峰值濃度降低約25%，且濃度波動較小，但最小血藥濃度並未顯著降低。[35][36]

在血液循環中，卡馬西平本身佔總殘留量的20%至30%，其餘的是代謝物，70%至80%的殘留物與血漿蛋白結合。母乳中的濃度是血漿中濃度的25%至60%。[36]

卡馬西平本身不具有藥理活性。它主要被CYP3A4激活，並生成卡馬西平-10,11-環氧化物，此環氧化物是抗癲癇作用的唯一來源。然後環氧化物被微粒體環氧化物水解酶 (mEH) 滅活，生成卡馬西平-反式-10,11-二醇，進一步再成為葡萄醣醛酸苷（英语：glucuronide）。其他代謝物有各種羥基衍生物和卡馬西平-N-葡萄醣醛酸苷。[36]

卡馬西平單次劑量給藥的生物半衰期約為35～40小時，但它是細胞色素P450酶的強誘導劑，重複給藥時的生物半衰期縮短至約12～17小時。其他酵素誘導劑如苯妥英或苯巴比妥可將半衰期進一步縮短至9-10小時。此藥物約有70%會經由尿液排出（幾乎全為代謝物形式），30%經由糞便排出。[35][36]

歷史

卡馬西平是1953年由在J.R. Geigy AG（後被藥業諾華併入）工作的瑞士化學家Walter Schindler所發現。[37][38]其於1963年首次作為治療癲癇的藥物在瑞士上市，商品名為Tegretol，同時又用於治療三叉神經痛。[37]英國自1965年起用其作抗癲癇藥，美國於1968年批准其用作醫療用途。[1]

此藥物在20世紀70年代一直被研究用於治療雙相情緒障礙症。[39]

目前市面已有此藥物的通用名藥物流通。[40]卡馬西平已被列入世界衛生組織基本藥物標準清單之中。[41]此藥物於2020年在美國最常用處方藥中排名第185，開立的處方箋超過200萬張。[42][43]

社會與文化

環境影響

主条目：藥物與個人護理用品對環境的影響

在美國污水處理廠的污水中[44]:224 以及接受污水處理廠排出水的溪流中可檢測出卡馬西平及其生物轉化產物的蹤跡。[45]相關機構已進行過現場和實驗室研究，以了解在摻有來自污水處理廠污泥的土壤中所生長的食品植物中此藥物的積累情況，及其隨著污泥中存在的藥物濃度和土壤中污泥成分的變化而變化的後續結果。於2014年所發表的一項審查，結論是"根據該研究結果，在用含有卡馬西平的生物固體所改良的土壤中生長的植物，其積累程度對人類健康構成微不足道的風險。"[44]:227

品牌名稱

卡馬西平在全球以許多品牌出售，Tegretol是其中之一。[46]

參見

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延伸閱讀

外部連結

维基共享资源上的相关多媒体资源：卡马西平
抗癫痫药 (N03)
GABA能药
其它
脂肪酸及其相关
其它
通道调节剂
其它
其它
其它
其它
描述
疾病
治療
抗驚厥劑（英语：Anticonvulsant）
非典型抗精神病藥
其它藥劑
钙 (Ca2+)
钾 (K+)
钠 (Na+)
其他

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