Elisaf Moses
Department of Internal Medicine, Medical School, University of Ioannina, Greece.
Curr Med Res Opin. 2002;18(5):269-76. doi: 10.1185/030079902125000516.
Fibric acid derivatives are a class of hypolipidaemic drugs used in the treatment of patients with hypertriglyceridaemia, mixed hyperlipidaemia and diabetic dyslipidaemia. Fibrate therapy results in a significant decrease in serum triglycerides and an increase in high-density lipoprotein (HDL) cholesterol levels. The latest drugs of this class are also effective in lowering low-density (LDL) cholesterol levels and can change the distribution of LDL towards higher and larger particles. The effects of fibrates on lipid metabolism are mostly mediated through the activation of peroxisome proliferator-activated receptors (PPARalpha). A number of angiographic and clinical trials have confirmed that fibrates can slow the progression of atherosclerotic disease and decrease cardiovascular morbidity and mortality. Recently published data suggest that the ability of fibrates to prevent atherosclerosis is not related only to their hypolipidaemic effects but also to other 'pleiotropic effects', such as their anti-inflammatory, antioxidant and antithrombotic effects, as well as their ability to improve endothelial function. Interestingly, fibrates may favourably influence the thrombotic/fibrinolytic system. In fact, most of these drugs can significantly decrease plasma fibrinogen levels and inhibit tissue factor expression and activity in human monocytes and macrophages. Some studies have shown that fibrates can improve carbohydrate metabolism in patients with dyslipidaemia, including diabetic patients. Among fibrates only fenofibrate can significantly decrease serum uric acid levels by increasing renal urate excretion. Fibrates, with the possible exception of gemfibrozil, can significantly increase serum creatinine and homocysteine levels. Finally, a reduction in serum alkaline phosphatase and gamma glutamyltranspeptidase (gammaGT) activity is a well-documented effect of therapy with fibrates. The fibrates are generally well-tolerated drugs with few side-effects. The most important side-effect is myositis, which is observed in patients with impaired renal function or when statins are given concomitantly.
纤维酸衍生物是一类用于治疗高甘油三酯血症、混合型高脂血症和糖尿病血脂异常患者的降血脂药物。贝特类药物治疗可使血清甘油三酯显著降低，高密度脂蛋白（HDL）胆固醇水平升高。这类最新的药物在降低低密度（LDL）胆固醇水平方面也很有效，并且可以使LDL的分布向更大颗粒转变。贝特类药物对脂质代谢的影响大多是通过激活过氧化物酶体增殖物激活受体（PPARα）介导的。多项血管造影和临床试验证实，贝特类药物可减缓动脉粥样硬化疾病的进展，降低心血管发病率和死亡率。最近发表的数据表明，贝特类药物预防动脉粥样硬化的能力不仅与其降血脂作用有关，还与其其他“多效性作用”有关，如抗炎、抗氧化和抗血栓作用，以及改善内皮功能的能力。有趣的是，贝特类药物可能对血栓形成/纤维蛋白溶解系统产生有利影响。事实上，这些药物大多可显著降低血浆纤维蛋白原水平，并抑制人单核细胞和巨噬细胞中组织因子的表达和活性。一些研究表明，贝特类药物可改善血脂异常患者（包括糖尿病患者）的碳水化合物代谢。在贝特类药物中，只有非诺贝特可通过增加肾脏尿酸排泄显著降低血清尿酸水平。除吉非贝齐外，贝特类药物可显著升高血清肌酐和同型半胱氨酸水平。最后，血清碱性磷酸酶和γ-谷氨酰转肽酶（γGT）活性降低是贝特类药物治疗的一个有充分记录的效果。贝特类药物通常耐受性良好，副作用较少。最重要的副作用是肌炎，在肾功能受损的患者或同时服用他汀类药物时会出现。
