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阿托伐他汀

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阿托伐他汀
临床资料
商品名英语Drug nomenclatureLipitor, Atorva
AHFS/Drugs.comMonograph
MedlinePlusa600045
核准状况
怀孕分级
  • : D
给药途径口服
ATC码
法律规范状态
法律规范
药物动力学数据
生物利用度12%
药物代谢肝脏 - CYP3A4
生物半衰期14小时
排泄途径胆汁
识别信息
  • (3R,5R)-7-[2-(4-Fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid
CAS号134523-00-5  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB配体ID
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.125.464 编辑维基数据链接
化学信息
化学式C33H35FN2O5
摩尔质量558.64
3D模型(JSmol英语JSmol
  • O=C(O)C[C@H](O)C[C@H](O)CCn2c(c(c(c2c1ccc(F)cc1)c3ccccc3)C(=O)Nc4ccccc4)C(C)C
  • InChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m1/s1 checkY
  • Key:XUKUURHRXDUEBC-KAYWLYCHSA-N checkY

阿托伐他汀INN:atorvastatin)商品名立普妥(Lipitor)、妥宁等,是一种他汀类药物,主要作用是降低血液胆固醇水平。它还可稳定血液斑块和预防中风,也可以用于减缓发烧(未批准用法)。类似于所有他汀类药物,阿托伐他汀通过抑制组织中,一种对胆固醇制造起关键作用的酵素——羟甲基戊二酸单酰辅酶A还原酶(HMG-CoA reductase),以减少体内制造胆固醇。

阿托伐他汀于1985年由布鲁斯·罗斯-帕克-戴维斯华纳-兰伯特公司(Bruce Roth of Parke-Davis Warner-Lambert Company)首次合成(现为辉瑞公司/Pfizer)[1],是制药历史上销售最好的药物。它自1996年被美国食品药品监督管理局批准以来,累计销售额超过1,250亿美元[2],并连续保持此销售冠军纪录达十年[3]。通用阿托伐他汀,由沃森制药公司英语Watson Pharmaceuticals兰伯西实验室制造,并于2011年11月30日开始于美国上市。2021年,它是美国第1常用的处方药。[4]

主治

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阿托伐他汀的主要用途是治疗血脂异常和预防心血管疾病[5]需要注意的是病人应在透过运动、减重与加强饮食等日常生活管理各方面都没法改善胆固醇水平的情形下,才服用阿托伐他汀。[5]

血脂异常

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心血管疾病

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伴随治疗的注意事项:可和胆汁酸树脂(离子交换树脂)相结合。不建议结合贝特类英语Fibrates(Fibrate)药物治疗, 因为增加与肌肉损伤相关的不良反应的风险[29]。根据患者年龄,药物剂量必须调整,降低肝功能不全。

禁忌

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服用阿托伐他汀期间必须注意有某些情况下可能出现横纹肌溶解症,一种可引起肌红蛋白尿症英语Myoglobinuria并导致急性肾衰竭的并发症。如果被怀疑或诊断为横纹肌溶解症,须立即停止阿托伐他汀治疗[30]。但实验显示,阿托伐他汀可能起到保护肾功能的作用[31]。另外,如果病人肌酸激酶(Creatine kinase,CK)的水平明显升高和怀疑有肌病英语Myopathy,也应停止使用阿托伐他汀。当与环孢素、贝特类(Fibrate)药物、红霉素烟酸抗真菌药共同给药有可能增加导致肌病的风险。[29]

怀孕期间是绝对禁止使用阿托伐他汀的,因为胆固醇是胎儿发育的必须生物合成途径,也包括类固醇细胞膜生成。另外也不建议喂哺母乳者服用此药,因为通过老鼠的实验表明阿托伐他汀可能会进入人类的乳汁分泌。[29]

副作用

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阿托伐他汀最严重副作用为肌酸激酶(CK)升高导致的肌病和横纹肌溶解症,虽然发生机会低于1%。[32][29]头痛是最常见的副作用,发生在10%的患者上。

其他副作用(发生几率在1–10%之间)包括:无力失眠头晕胸部疼痛外周性水肿皮疹腹痛便秘腹泻消化不良胃肠胀气恶心泌尿道感染关节痛肌肉痛背痛关节炎鼻窦炎咽炎支气管炎鼻炎、感染、流感样综合征和过敏性反应。[29]

小部分服用本药和/或其它他汀类药物病者曾引致失忆,特别是女性。因胆固醇的合成,是正常的神经元功能所必需的。但据辉瑞公司的临床试验,“胆固清没有和失忆之间有因果关系。[33][34][35]

在少数情况下,谷丙转氨酶(ALT)和天冬氨酸氨基转移酶(AST)水平会升高。[36]

有报告指出高剂量阿托伐他汀能使血糖控制恶化。[37]

药物和食物的相互作用

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此药物和安妥明英语Clofibrate(Clofibrate)、非诺贝特(Fenofibrate)、吉非贝齐英语Gemfibrozil(Gemfibrozil)(一些治疗高胆固醇血症药物)有相互作用,可增加引致肌病和横纹肌溶解症风险。[38][39]

和CYP3A4抑制剂(伊曲康唑,泰利和伏立康唑)共同用药,可能会导致不良反应。和CYP3A4诱导剂(波生坦,磷苯妥英钠,苯妥英)联合用药,可能减少阿托伐他汀的血液浓度。烟酸也被证明增加肌病或横纹肌溶解症的风险。他汀也能令其他药物(如华法林地高辛)的浓度发生改变。补充维生素D可降低阿托伐他汀和活性代谢物浓度。

葡萄柚汁是肠道CYP3A4的抑制剂,葡萄柚汁与阿托伐他汀共服可能会导致Cmax和AUC增加,从而导致不良反应或药物过量并产生毒性。[36][33][40][41]

作用机理

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阿托伐他汀是HMG-CoA还原酶的竞争性抑制剂,这与其他他汀类药物相似,但不同的是本药为一个完全人工合成的化合物。 HMG-CoA还原酶催化还原3-羟基-3-甲基-辅酶A(HMG-COA)成为甲羟戊酸,这是肝脏胆固醇生物合成的速率控制步骤(rate-limiting step)。通过抑制这种酵素,降低从头合成胆固醇,增加肝细胞上的低密度脂蛋白受体LDL受体),增加肝细胞对低密度脂蛋白的吸收,降低血液中的低密度脂蛋白胆固醇量。像其他他汀类药物,阿托伐他汀也降低血液甘油三酯水平,并略有增加高密度脂蛋白胆固醇水平。

药代动力学

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口服阿托伐他汀吸收迅速,最大血药浓度1至2小时。该药物的绝对生物利用度约为14%。阿托伐他汀通过肠道时经历首过效应,这是此药的生物利用度低的主要原因。尽管当阿托伐他汀与食物一起服用时,其降低血液LDL(低密度脂蛋白)的效用并没因此减少,但与食物共服,药物Cmax(吸收率)减少25%,AUC(吸收程度)减少9%;而夜间服药Cmax(吸收率)和AUC(吸收程度)减少30%,但都不会影响阿托伐他汀的疗效。

阿托伐他汀的蛋白结合率高(≥98%),阿托伐他汀代谢主要通过细胞色素P450-3A4羟基形成。以激活邻位类羟基化代谢物和β-氧化代谢物。前者对全身的HMG-CoA还原酶运作起关键效用。邻羟基代谢物进一步透过葡糖醛酸代谢作用英语Glucuronidation代谢。细胞色素P450的抑制剂和诱导剂分别能增加或减少此药的血药浓度,这已被一项以红霉素(一种已知的细胞色素P450抑制剂)与阿托伐他汀为对象的实验室试验中被验证。

阿托伐他汀主要是经肝胆汁排泄,阿托伐他汀在尿液中回收的不到2%,没有进入肠肝循环。阿托伐他汀消除半衰期约14小时。值得注意的是,HMG-CoA还原酶抑制活性有半衰期20至30小时,这被认为是与活性代谢产物有关。阿托伐他汀也是肠道P-糖蛋白英语P-glycoprotein外排转运,在药物正在肠脏被吸收时被泵回肠腔中。[42]

功能不全患者,血药浓度受到肝脏疾病显著影响。与A-末期肝病患者Cmax和AUC增加4倍。B超末期肝病患者的Cmax增加16倍、AUC增加11倍。老年患者(65岁以上)药代动力学表现与年轻成年人不同,老年患者的AUC和Cmax值分别提高40%和30%;而健康长者对药物反应较理想,故可能只需处方较低剂量予此人群。[29][43][44]

药理学

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阿托伐他汀一些基因多态性(Genetic polymorphism)已被发现与本药不良副作用的发生率较高有关。这种现象被怀疑与血浆中的药理活性代谢产物增加有关,如阿托伐他汀内酯和P-Hydroxyatorvastatin。对于较可能诱发不良副作用的潜在患者,可使用特定的色谱技术对阿托伐他汀及其活性代谢物进行监测。[45]

配方

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辉瑞生产的阿托伐他汀钙片

阿托伐他汀钙片由辉瑞公司销售。药片为白色、椭圆形的薄膜包衣片。辉瑞公司还与其他药物打包结合,如Caduet。辉瑞公司建议服食者不要将药片一分为二。

参考

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  1. ^ http://www.lipitor.com/页面存档备份,存于互联网档案馆) Pfizer product promotion page (Liptor)
  2. ^ http://www.crainsnewyork.com/article/20111228/HEALTH_CARE/111229902页面存档备份,存于互联网档案馆) Crain's New York Business. 2011-12-28.
  3. ^ http://www.nytimes.com/2011/11/12/health/plan-would-delay-sales-of-generic-for-lipitor.html页面存档备份,存于互联网档案馆) New York Times.
  4. ^ [The Top 300 Drugs of 2021 https://web.archive.org/web/20210212142534/https://clincalc.com/DrugStats/Top300Drugs.aspx]
  5. ^ 5.0 5.1 Atorvastatin Calcium页面存档备份,存于互联网档案馆) Drugs.com. Retrieved 3 April 2011.
  6. ^ 6.0 6.1 6.2 McCrindle BW, Ose L, Marais AD. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J. Pediatr. July 2003, 143 (1): 74–80. PMID 12915827. doi:10.1016/S0022-3476(03)00186-0. 
  7. ^ Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004, 364 (9435): 685–96. PMID 15325833. doi:10.1016/S0140-6736(04)16895-5. 
  8. ^ Backman JT, Luurila H, Neuvonen M, Neuvonen PJ. Rifampin markedly decreases and gemfibrozil increases the plasma concentrations of atorvastatin and its metabolites. Clin. Pharmacol. Ther. August 2005, 78 (2): 154–67. PMID 16084850. doi:10.1016/j.clpt.2005.04.007. 
  9. ^ Hermann M, Bogsrud MP, Molden E, Asberg A, Mohebi BU, Ose L, Retterstøl K. Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy. Clin. Pharmacol. Ther. June 2006, 79 (6): 532–9. PMID 16765141. doi:10.1016/j.clpt.2006.02.014. 
  10. ^ Ozaki K, Kubo T, Imaki R, Shinagawa H, Fukaya H, Ohtaki K, Ozaki S, Izumi T, Aizawa Y. The anti-atherosclerotic effects of lipid lowering with atorvastatin in patients with hypercholesterolemia. J. Atheroscler. Thromb. August 2006, 13 (4): 216–9 [2014-02-16]. PMID 16908955. doi:10.5551/jat.13.216. (原始内容存档于2019-12-05). 
  11. ^ Marais AD, Firth JC, Bateman ME, Byrnes P, Martens C, Mountney J. Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. August 1997, 17 (8): 1527–31. PMID 9301631. doi:10.1161/01.ATV.17.8.1527. 
  12. ^ McCrindle BW, Ose L, Marais AD (July 2003). "Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial". J. Pediatr. 143 (1): 74–80. DOI:10.1016/S0022-3476(03)00186-0. PMID 12915827.
  13. ^ Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM (April 2006). "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial". Journal of the American Medical Association 295 (13): 1556–65. DOI:10.1001/jama.295.13.jpc60002. PMID 16533939.
  14. ^ 14.0 14.1 Nawrocki JW, Weiss SR, Davidson MH, Sprecher DL, Schwartz SL, Lupien PJ, Jones PH, Haber HE, Black DM (May 1995). "Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor". Arterioscler. Thromb. Vasc. Biol. 15 (5): 678–82. DOI:10.1161/01.ATV.15.5.678. PMID 7749881.
  15. ^ Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, Keilson LM, Brown WV, Miller VT, Shurzinske LJ, Black DM (January 1996). "Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia". Journal of the American Medical Association 275 (2): 128–33. DOI:10.1001/jama.275.2.128. PMID 8531308.
  16. ^ Marais AD, Firth JC, Bateman ME, Byrnes P, Martens C, Mountney J (August 1997). "Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia". Arterioscler. Thromb. Vasc. Biol. 17 (8): 1527–31. DOI:10.1161/01.ATV.17.8.1527. PMID 9301631.
  17. ^ Rossi S, ed. (2006). Australian medicines handbook 2006. Adelaide, S. Aust: Australian Medicines Handbook Pty Ltd. ISBN 978-0-9757919-2-9.
  18. ^ Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. April 2003, 361 (9364): 1149–58. PMID 12686036. doi:10.1016/S0140-6736(03)12948-0. 
  19. ^ Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. June 2003, 326 (7404): 1423. PMC 162260可免费查阅. PMID 12829554. doi:10.1136/bmj.326.7404.1423. 
  20. ^ Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories (PDF). Circulation. May 1998, 97 (18): 1837–47 [2014-02-16]. PMID 9603539. doi:10.1161/01.CIR.97.18.1837. (原始内容存档 (PDF)于2011-09-19). 
  21. ^ Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). American Journal of Cardiology. March 1998, 81 (5): 582–7. PMID 9514454. doi:10.1016/S0002-9149(97)00965-X. 
  22. ^ Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J (April 2003). "Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial". Lancet 361 (9364): 1149–58. DOI:10.1016/S0140-6736(03)12948-0. PMID 12686036.
  23. ^ Law MR, Wald NJ, Rudnicka AR (June 2003). "Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis". BMJ 326 (7404): 1423. DOI:10.1136/bmj.326.7404.1423. PMC 162260. PMID 12829554.
  24. ^ Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (May 1998). "Prediction of coronary heart disease using risk factor categories". Circulation 97 (18): 1837–47. DOI:10.1161/01.CIR.97.18.1837. PMID 9603539.
  25. ^ Jones P, Kafonek S, Laurora I, Hunninghake D (March 1998). "Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study)". American Journal of Cardiology 81 (5): 582–7. DOI:10.1016/S0002-9149(97)00965-X. PMID 9514454.
  26. ^ Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH (2004). "Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial". Lancet 364 (9435): 685–96. DOI:10.1016/S0140-6736(04)16895-5.
  27. ^ eil HA, DeMicco DA, Luo D, Betteridge DJ, Colhoun HM, Durrington PN, Livingstone SJ, Fuller JH, Hitman GA (November 2006). "Analysis of efficacy and safety in patients aged 65-75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS)". Diabetes Care 29 (11): 2378–84. DOI:10.2337/dc06-0872.
  28. ^ Gentile S, Turco S, Guarino G, Sasso CF, Amodio M, Magliano P, Salvatore T, Corigliano G, Agrusta M, De Simone G, Gaeta I, Oliviero B, Torella R (December 2000). "Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia". Diabetes Obes Metab
  29. ^ 29.0 29.1 29.2 29.3 29.4 29.5 Lipitor: Prescribing Information页面存档备份,存于互联网档案馆). Pfizer. June 2009.
  30. ^ Hermann M, Bogsrud MP, Molden E, Asberg A, Mohebi BU, Ose L, Retterstøl K (June 2006). "Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy". Clin. Pharmacol. Ther. 79 (6): 532–9. DOI:10.1016/j.clpt.2006.02.014. PMID 16765141.
  31. ^ Williams D, Feely J (2002). "Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors". Clin Pharmacokinet 41 (5): 343–70. DOI:10.2165/00003088-200241050-00003. PMID 12036392.
  32. ^ Rossi S (编). Australian medicines handbook 2006. Adelaide, S. Aust: Australian Medicines Handbook Pty Ltd. 2006. ISBN 0-9757919-2-3. 
  33. ^ 33.0 33.1 Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM (July 2003). "Statin-associated memory loss: analysis of 60 case reports and review of the literature". Pharmacotherapy 23 (7): 871–80. DOI:10.1592/phco.23.7.871.32720. PMID 12885101.
  34. ^ The side effects of statins: Heart healthy and head harmful?". Michael O'Riordan. HeartWire. 12 February 2008. Retrieved 22 October 2010
  35. ^ O'Riordan M (2010-10-22). "The side effects of statins: Heart healthy and head harmful?". The Wall Street Journal. Retrieved 2010-10-24.
  36. ^ 36.0 36.1 Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco AV, Littarru GP (March 1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol 33 (3): 226–9. PMID 8463436.
  37. ^ Kostapanos MS, Liamis GL, Milionis HJ, Elisaf MS. Do statins beneficially or adversely affect glucose homeostasis?. Curr Vasc Pharmacol. September 2010, 8 (5): 612–31. PMID 20507274. doi:10.2174/157016110792006879. 
  38. ^ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco AV, Littarru GP. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol. March 1993, 33 (3): 226–9. PMID 8463436. doi:10.1002/j.1552-4604.1993.tb03948.x. 
  39. ^ Steiner G. Atherosclerosis in type 2 diabetes: a role for fibrate therapy?. Diab Vasc Dis Res. December 2007, 4 (4): 368–74. PMID 18158710. doi:10.3132/dvdr.2007.067. 
  40. ^ "The side effects of statins: Heart healthy and head harmful?". Michael O'Riordan. HeartWire. 12 February 2008. Retrieved 22 October 2010
  41. ^ http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c6e131fe-e7df-4876-83f7-9156fc4e8228页面存档备份,存于互联网档案馆) U.S. National Library of Medicine.
  42. ^ Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet. 2002, 41 (5): 343–70. PMID 12036392. doi:10.2165/00003088-200241050-00003. 
  43. ^ Villa J, Pratley RE (June 2010). "Ezetimibe/simvastatin or atorvastatin for the treatment of hypercholesterolemia in patients with the metabolic syndrome: the VYMET study". Curr. Diab. Rep. 10 (3): 173–5. DOI:10.1007/s11892-010-0107-5. PMID 20425579.
  44. ^ McCormack T, Harvey P, Gaunt R, Allgar V, Chipperfield R, Robinson P (July 2010). "Incremental cholesterol reduction with ezetimibe/simvastatin, atorvastatin and rosuvastatin in UK General Practice (IN-PRACTICE): randomised controlled trial of achievement of Joint British Societies (JBS-2) cholesterol targets". Int. J. Clin. Pract. 64 (8): 1052–61. DOI:10.1111/j.1742-1241.2010.02429.x. PMID 20487050.
  45. ^ Deshmukh HA, Colhoun HM, Johnson T, McKeigue PM, Betteridge DJ, Durrington PN, Fuller JH, Livingstone S, Charlton-Menys V, Neil A, Poulter N, Sever P, Shields DC, Stanton AV, Chatterjee A, Hyde C, Calle RA, Demicco DA, Trompet S, Postmus I, Ford I, Jukema JW, Caulfield M, Hitman GA (May 2012). "Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a)". J Lipid Res 53 (5): 1000–1011. DOI:10.1194/jlr.P021113. PMID 22368281.

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