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Microsomal transfer protein inhibition in humans

机译:抑制微粒体转移蛋白

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Purpose of review Microsomal triglyceride transfer protein (MTP) is a key protein in the secretion of apolipoprotein B-containing lipoproteins. Its pharmacological inhibition is associated with a decrease in LDL cholesterol (LDL-C) and triglycerides. However, the clinical use of MTP inhibitors has been uncertain because of the gastrointestinal adverse events and the increase in liver fat content observed during their administration. Recent findings Lomitapide, a systemic MTP inhibitor, significantly reduces LDL-C in homozygous familial hypercholesterolemia (hoFH) when administered concurrently with other lipid-lowering therapies, including apheresis. Its lipid-lowering effect is additive to that of existing drugs. In the presence of an up-titration regiment and low-fat diet, lomitapide is generally well tolerated and liver fat accumulation stabilizes after the initial increase. Elevation of alanine aminotranferase levels greater than 3 times the upper limit of normal can be managed successfully with temporary dose reduction. Drug-drug interaction studies show that concomitant treatment of lomitapide with other lipid-lowering drugs is generally safe. Based on these findings, lomitapide was recently approved for the treatment of hoFH as add-on therapy. Summary MTP inhibition is a valuable therapeutic approach for hoFH. Long-term safety consequences of liver fat accumulation will need to be assessed.
机译:综述目的微粒体甘油三酸酯转移蛋白(MTP)是分泌载脂蛋白B的脂蛋白中的关键蛋白。它的药理抑制作用与降低LDL胆固醇(LDL-C)和甘油三酸酯有关。然而,由于胃肠道不良事件和在给药过程中观察到的肝脂肪含量增加,MTP抑制剂的临床应用尚不确定。最新发现Lomitapide是一种全身性MTP抑制剂,与其他血脂降低疗法(包括血液分离术)同时使用时,可明显降低纯合子家族性高胆固醇血症(hoFH)中的LDL-C。它的降脂作用是现有药物的附加作用。在高剂量方案和低脂饮食的情况下,洛米他肽通常耐受性良好,初始增加后肝脂肪蓄积稳定。暂时减少剂量可成功控制丙氨酸氨基转移酶水平的升高超过正常上限的3倍。药物相互作用研究表明,与其他降脂药物同时治疗洛米他肽通常是安全的。基于这些发现,洛米他滨最近被批准用于hoFH的附加治疗。总结MTP抑制是hoFH有价值的治疗方法。肝脂肪积聚的长期安全后果将需要评估。

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