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{{Drugbox | verifiedrevid = 458281479 | IUPAC_name = hydroxyurea | image = Hydroxyurea.png | width = 180 | alt = Structural formula | image2 = Hydroxyurea-3D-balls.png <!--Clinical data--> | tradename = Apo-Hydroxyurea, Droxia, Hydrea | Drugs.com = {{drugs.com|international|hydroxycarbamide}} | MedlinePlus = a682004 | pregnancy_category = D (USA)<ref name=Liebelt2007/> | legal_status = Rx-only | routes_of_administration = 口服 <!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = [[肝脏]] | elimination_half-life = 3-4小时 | excretion = [[肾脏]]与[[肺]] <!--Identifiers--> | CASNo_Ref = {{cascite|correct|CAS}} | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 127-07-1 | ATC_prefix = L01 | ATC_suffix = XX05 | ATC_supplemental = | PubChem = 3657 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01005 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 3530 | NIAID_ChemDB = 006310 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = X6Q56QN5QC | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00341 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 44423 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 467 <!--Chemical data--> | C=1 | H=4 | N=2 | O=2 | molecular_weight = 76.0547 g/mol | smiles = O=C(N)NO | InChI = 1/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4) | InChIKey = VSNHCAURESNICA-UHFFFAOYAY | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VSNHCAURESNICA-UHFFFAOYSA-N }} '''羟基脲'''（[[国际非专利药品名称|INN]]：'''Hydroxycarbamide'''，又名'''Hydroxyurea'''，商品名包括'''Hydrea'''和'''Droxia'''）是一种[[化疗]]及抗[[逆转录病毒]]药物，被用于治疗[[慢性粒细胞白血病]]、[[骨髓增生性疾病]]和镰刀型[[细胞]][[贫血症]]等疾病。 ==作用机理== 羟基脲的其中一种普遍接受的机理是它能够通过清除酪[[氨酰]][[自由基]]来抑制[[核糖核苷酸]][[二磷酸]][[还原酶]]，从而阻碍[[脱氧核糖核苷酸]]的合成。<ref>{{DorlandsDict|four/000050608|hydroxyurea}}</ref><ref name=Platt2008>{{cite journal |author=Platt OS |title=Hydroxyurea for the treatment of sickle cell anemia |journal=N. Engl. J. Med. |volume=358 |issue=13 |pages=1362–9 |year=2008 |pmid=18367739 |doi=10.1056/NEJMct0708272}}</ref> 在镰刀型细胞贫血症的治疗中，羟基脲能够增加[[胎儿血红蛋白]]的浓度。这点的具体作用机理仍不清楚，但有研究认为羟基脲能够增加[[一氧化氮]]的浓度，从而激活[[鸟苷酸]][[环化酶]]，进而增加[[环磷酸鸟苷]]的浓度，激活胎儿血红蛋白所需的[[丙种球蛋白]]的合成，同时清除快速分裂的产生镰刀型[[血红蛋白]]的细胞。<ref name=Platt2008/><ref name="pmid12531879">{{cite journal |author=Cokic VP, Smith RD, Beleslin-Cokic BB, ''et al.'' |title=Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase |journal=J Clin Invest |volume=111 |issue=2 |pages=231–9 |year=2003 |pmid=12531879 |doi=10.1172/JCI16672|url=http://www.jci.org/articles/view/16672 |pmc=151872}} {{PMC|151872}}</ref> ==用途== 羟基脲被用于治疗以下疾病： * 骨髓增生性疾病（主要是[[真性红细胞增多症]]和[[原发性血小板增多症]]）<ref name="pmid16000354">{{cite journal |author=Harrison CN, Campbell PJ, Buck G, ''et al.'' |title=Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia |journal=N. Engl. J. Med. |volume=353 |issue=1 |pages=33–45 |year=2005 |month=July |pmid=16000354 |doi=10.1056/NEJMoa043800 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16000354&promo=ONFLNS19}}</ref> * 镰刀型细胞贫血症（能够减少发作时患者的疼痛）<ref name="pmid18458272">{{cite journal |author=Lanzkron S, Strouse JJ, Wilson R, ''et al.'' |title=Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease |journal=Ann. Intern. Med. |volume=148 |issue=12 |pages=939–55 |year=2008 |month=June |pmid=18458272 |doi= |url=}}</ref> * [[艾滋病]]（用于在抗[[逆转录病毒]]疗法辅助[[去羟肌苷]]）<ref name="pmid15597521">{{cite journal |author=Frank I, Bosch RJ, Fiscus S, ''et al.'' |title=Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307 |journal=AIDS Res. Hum. Retroviruses |volume=20 |issue=9 |pages=916–26 |year=2004 |month=September |pmid=15597521 |doi= 10.1089/aid.2004.20.916|url=}}</ref> * [[银屑病]]的二线治疗（能够减缓[[皮肤细胞]]的快速分裂）<ref name="pmid17642550">{{cite journal |author=Sharma VK, Dutta B, Ramam M |title=Hydroxyurea as an alternative therapy for psoriasis |journal=Indian J Dermatol Venereol Leprol |volume=70 |issue=1 |pages=13–7 |year=2004 |pmid=17642550 |doi= |url=http://www.ijdvl.com/article.asp?issn=0378-6323;year=2004;volume=70;issue=1;spage=13;epage=17;aulast=Sharma}}</ref> * [[肥大细胞增多症]]<ref>{{Cite journal | last1 = Escribano | first1 = L. | last2 = Álvarez-Twose | first2 = I. N. | last3 = Sánchez-Muñoz | first3 = L. | last4 = Garcia-Montero | first4 = A. | last5 = Núñez | first5 = R. | last6 = Almeida | first6 = J. | last7 = Jara-Acevedo | first7 = M. | last8 = Teodósio | first8 = C. | last9 = García-Cosío | first9 = M. N. | doi = 10.1016/j.jaci.2009.05.003 | title = Prognosis in adult indolent systemic mastocytosis: A long-term study of the Spanish Network on Mastocytosis in a series of 145 patients | journal = Journal of Allergy and Clinical Immunology | volume = 124 | issue = 3 | pages = 514–521 | year = 2009 | pmid = 19541349 | pmc = }}</ref> *[[慢性粒细胞白血病]]（基本上被[[伊马替尼]]所代替，但仍因其高性价比而被使用）<ref>{{Cite journal | last1 = Dalziel | first1 = K. | last2 = Round | first2 = A. | last3 = Stein | first3 = K. | last4 = Garside | first4 = R. | last5 = Price | first5 = A. | title = Effectiveness and cost-effectiveness of imatinib for first-line treatment of chronic myeloid leukaemia in chronic phase: A systematic review and economic analysis | journal = Health technology assessment (Winchester, England) | volume = 8 | issue = 28 | pages = iii, ii1–120 | year = 2004 | pmid = 15245690 }}</ref> *[[头颈癌]]（单独给药或与[[放疗]]合用） *[[卵巢癌]]（同上） 除此之外，羟基脲还在[[生物化学]]研究上被用作[[DNA复制]][[抑制剂]]，因为它能够消耗脱氧核糖核苷酸而引起[[DNA]]双链在[[复制叉]]附近断裂（见[[DNA修复]]）。<ref name="pmid14573610">{{cite journal |author=Koç A, Wheeler LJ, Mathews CK, Merrill GF |title=Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools |journal=J. Biol. Chem. |volume=279 |issue=1 |pages=223–30 |year=2004 |month=January |pmid=14573610 |doi=10.1074/jbc.M303952200 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=14573610}}</ref> ==剂量== 剂量因情况而异。在骨髓增生性疾病中，一般来说是每日30mg~40mg/kg；剂量的增加与减少由[[血细胞计数]]变化及是否发生[[骨髓抑制]]而定。<ref name="gale" /> 对于镰刀型细胞贫血症，起始剂量为15mg/kg（[[肾功能]]减弱者则酌情减少）；两周之后预期血红蛋白和[[血小板计数]]将会减少，而[[平均红细胞体积]]会增加。之后的剂量在密切观察[[全血细胞计数]]的同时每两周增加一次，直至剂量达到35mg/kg或[[血球]]减少发生。<ref name=Platt2008/> ==[[副作用]]== 有报导的副作用包括：[[嗜睡]]、[[恶心]]、[[呕吐]]、[[腹泻]]、[[便秘]]、[[食欲不振]]、粘膜炎、[[胃炎]]、骨髓抑制（剂量限制性[[毒性]]；停药后1~3周可恢复）、[[脱发]]、[[皮肤]]变化、[[肝功能测试|肝功能]]异常、[[肾功能异常]]（[[肌酐]]和尿氮升高）。<ref name=Liebelt2007>{{Cite journal| doi = 10.1002/bdrb.20123| pmid = 17712860| year = 2007| last1 = Liebelt | first1 = E.| last2 = Balk | first2 = S.| last3 = Faber | first3 = W.| last4 = Fisher | first4 = J.| last5 = Hughes | first5 = C.| last6 = Lanzkron | first6 = S. | last7 = Lewis | first7 = K. | last8 = Marchetti | first8 = F.| last9 = Mehendale | first9 = H. | title = NTP-CERHR expert panel report on the reproductive and developmental toxicity of hydroxyurea | volume = 80 | issue = 4 | pages = 259–366 | journal = Birth defects research. Part B, Developmental and reproductive toxicology }}</ref> 由于羟基脲的[[骨髓]]毒性，治疗时必须密切观察全血细胞计数，且应及时应对由于[[白细胞]]水平下降而引起的[[感染]]。除此之外，肝肾功能、[[尿酸]]和[[电解质]]也需经常检查。<ref name="gale">{{Cite book|last=Thackery |first=Ellen |title=The Gale Encyclopedia of Cancer: A-K |publisher=Thomson Gale |location=Detroit |year=2002 |page=514-516 |isbn=0-7876-5610-0}}</ref> 羟基脲主要用于治疗的骨髓增生性疾病大部分都有转化为[[急性粒细胞白血病]]的可能性。长期以来人们一直担心羟基脲本身也会引起[[白血病]]，但研究显示这种可能性很小或者基本上不存在。然而，这仍然阻碍了它在镰刀型贫血症上的进一步应用。<ref name=Platt2008/> ==合成== 羟基脲由Dresler和Stein在1869年通过羟胺、[[盐酸]]和氰化钾反应合成；目前工业上生产则使用羟胺和氰酸。<ref>{{cite journal | doi = 10.1016/S0950-4230(02)00044-X | title = Hydroxyurea explosion: a thermoanalytical and calorimetric study | year = 2002 | last1 = Lunghi | first1 = A | last2 = Aloni | first2 = C | last3 = Gigante | first3 = L | last4 = Mazzei | first4 = N | last5 = Cardillo | first5 = P | journal = Journal of Loss Prevention in the Process Industries | volume = 15 | issue = 6 | pages = 489–495 }}</ref> 羟基脲也能由[[氨基甲酸乙酯]]与羟胺通过取代反应合成。<ref>{{OrgSynth | author = R. Deghenghi | collvol = 5 | collvolpages = 645 | prep = cv5p0645 | year = 1973 | title = Hydroxyurea}}</ref> ==参看== *[[药理学/羟基脲|《药理学》- 羟基脲]] ==参考资料== {{reflist|2}} [[Category:脲]] [[Category:抗肿瘤抗代谢物]] [[Category:IARC第3类致癌物质]] ==参考来源== *[http://zh.wikipedia.org/wiki/%E7%BE%9F%E5%9F%BA%E8%84%B2 维基百科-羟基脲] {{导航板-中国国家基本药物目录2012版入选药品}} {{导航板-世界卫生组织基本药物标准清单入选药品}} {{导航板-化疗药物}} {{抗逆转录病毒药物}}

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