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[新型抗血脂药:前景]

[New antilipemics: prospects].

作者信息

Farnier Michel

出版信息

Therapie. 2003 Jan-Feb;58(1):97-105. doi: 10.2515/therapie:2003014.

Abstract

The field of new lipid-lowering drug research is very active, with researchers, looking to make the currently available drugs more powerful and safer, and to develop new classes of drugs. Among the statins, development has gone the farthest for rosuvastatin and pitavastatin. Colesevelam is a new bile acid sequestrant with a better digestive tolerance. Among the new classes of drugs, the most promising molecules are the cholesterol absorption inhibitors--with ezetimibe as the first in line--and the PPAR-alpha and PPAR-gamma activators. Among the other classes, the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, and ileal bile acid transporter inhibitors, have to be mentioned. In most of the cases, those new compounds are being developed mainly as a combined treatment with statins. However, these combination therapies differ depending on the lipid abnormalities of the patient. The statin-ezitimibe and the statin-bile acid sequestrant combinations have been the most studied treatments in pure hypercholesterolaemia. On another hand, the statin-PPAR-alpha and -gamma activator combination were the first to be developed for patients with combined hyperlipidaemia or type 2 diabetes mellitus. However, the clinical benefit of ACAT or CETP inhibitors remains to be determined and the development of MTP inhibitors has been restricted so far, because of problems of digestive intolerance and hepatic steatosis. Finally, the discovery of new specific lipoprotein receptors, such as the ABCA1 and SRB1 receptors, means that we can work towards developing new potential targets for pharmacological intervention.

摘要

新型降脂药物的研究领域十分活跃,研究人员致力于让现有药物效果更强、更安全,并研发新型药物。在他汀类药物中,瑞舒伐他汀和匹伐他汀的研发进展最为显著。考来维仑是一种新型胆汁酸螯合剂,具有更好的消化耐受性。在新型药物类别中,最具潜力的分子是胆固醇吸收抑制剂(依泽替米贝是其中的佼佼者)以及PPAR-α和PPAR-γ激动剂。在其他类别中,还不得不提及酰基辅酶A:胆固醇酰基转移酶(ACAT)抑制剂、微粒体甘油三酯转移蛋白(MTP)抑制剂、胆固醇酯转移蛋白(CETP)抑制剂和回肠胆汁酸转运体抑制剂。在大多数情况下,这些新化合物主要作为与他汀类药物的联合治疗药物来研发。然而,这些联合疗法会因患者的血脂异常情况而有所不同。他汀类药物与依泽替米贝以及他汀类药物与胆汁酸螯合剂的联合疗法,是在单纯高胆固醇血症中研究最多的治疗方法。另一方面,他汀类药物与PPAR-α和-γ激动剂的联合疗法是最早为混合型高脂血症或2型糖尿病患者研发的。然而,ACAT或CETP抑制剂的临床益处仍有待确定,并且由于消化不耐受和肝脂肪变性问题,MTP抑制剂的研发至今受到限制。最后,新的特异性脂蛋白受体的发现,如ABCA1和SRB1受体,意味着我们可以朝着开发新的药理学干预潜在靶点努力。

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