Schmitz Gerd, Schmitz-Madry Anna, Ugocsai Peter
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Curr Opin Lipidol. 2007 Apr;18(2):164-73. doi: 10.1097/MOL.0b013e3280555083.
To summarize recent findings on pharmacokinetics, pharmacodynamics, drug-drug interactions and influence of lifestyle heterogeneity on adverse events in cholesterol-lowering therapy
The prevention of cardiovascular disease is critically dependent on lipid-lowery therapy, including statins, cholesterol absorption inhibitors, fibrates and nicotinic acid. Statins are the most prescribed drugs in lipid lowering therapy with variability in response and almost one third of the patients do not meet their treatment goals. The severe adverse effects of treatment with cerivastatin stimulated the search for new genes and gene variations affecting pharmacokinetics, drug-drug interactions and pharmacodynamics. Moreover, instead of monotherapy, combined therapy of statins with ezetemibe and niacin was considered. This led to the identification of CD13, NPC1L1 and HM74A as new targets and CYP2C8 and glucuronidation enzymes as potential targets for drug-drug interactions. Moreover multiple polymorphic sites and pleiotrophic gene targets were reinvestigated in larger cohorts and the relevant pathogenetic factors start to evolve.
Statin therapy is widely used and well tolerated by the majority of patients. To further reduce potential adverse effects and to increase efficacy, combined therapy concepts with ezetimibe or niacin are underway.
总结胆固醇降低治疗中药物动力学、药效学、药物相互作用以及生活方式异质性对不良事件影响的近期研究结果。
心血管疾病的预防严重依赖于降脂治疗，包括他汀类药物、胆固醇吸收抑制剂、贝特类药物和烟酸。他汀类药物是降脂治疗中处方最多的药物，其疗效存在差异，近三分之一的患者未达到治疗目标。西立伐他汀治疗的严重不良反应促使人们寻找影响药物动力学、药物相互作用和药效学的新基因和基因变异。此外，除了单一疗法，还考虑了他汀类药物与依泽替米贝和烟酸的联合治疗。这导致将CD13、NPC1L1和HM74A确定为新靶点，将CYP2C8和葡萄糖醛酸化酶确定为药物相互作用的潜在靶点。此外，在更大的队列中对多个多态性位点和多效性基因靶点进行了重新研究，相关致病因素开始逐渐明晰。
他汀类药物治疗被广泛应用，大多数患者耐受性良好。为了进一步降低潜在不良反应并提高疗效，正在开展依泽替米贝或烟酸联合治疗方案。
