Prolonged cholestasis after raloxifene and fenofibrate interaction： A case report

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.     

自体外周血内皮祖细胞移植联合PPAR激动剂治疗大鼠急性心肌梗死的实验研究

目的探讨自体外周血内皮祖细胞（EPCs）移植联合PPAR激动剂罗格列酮、非诺贝特治疗大鼠急性心肌梗死的可行性和疗效。方法40只SD雄性大鼠随机分为四组：心肌梗死对照组（组Ⅰ）、单纯EPCs移植组（组Ⅱ）、EPCs移植联合罗格列酮治疗组（组Ⅲ）、内皮祖细胞移植联合非诺贝特治疗组（组Ⅳ）,每组10只。应用密度梯度离心法获得大鼠外周血单个核细胞,体外培养扩增获得较纯的EPCs后,移植到大鼠急性心肌梗死模型梗死区,罗格列酮组、非诺贝特组分别以罗格列酮（20mg·kg^-1·d^-1）和非诺贝特（20mg·kg^-1·d^-1）灌胃。8周后超声心动图检测大鼠心功能改变,测定血流动力学指标,免疫组化观察心肌内移植EPCs及大鼠心肌修复情况。结果细胞移植8周后,组Ⅱ、组Ⅲ和组Ⅳ大鼠心功能,左室收缩舒张功能较组Ⅰ明显改善（P〈0．05）,且组Ⅲ和组Ⅳ改变更显著（P〈0．05）。结论EPCs移植可以显著改善急性心肌梗死大鼠的心功能,EPCs移植联用罗格列酮和非诺贝特,优于单独应用EPCs移植。     

非诺贝特致甲状腺功能减低患者横纹肌溶解症1例

1例37a男性患者,因血脂高,给予非诺贝特缓释胶囊250mg,口服,每晚1次。服药前查：TG17.17mmol·L-1,CK45U·L-1,LDH98U·L-1,AST30IU·L-1,ALT21IU·L-1。服药第9天后患者出现右侧小腿肌肉酸痛、无力,急查CK2900.05U·L-1,LDH432U·L-1,AST121IU·L-1,ALT65.5IU·L-1,确诊为横纹肌溶解症。立即停用非诺贝特,给予碱化尿液、保护细胞膜等治疗。查甲状腺功能示：TT30.3nmol·L-1,TT47.5nmol·L-1,FT31.9pmol·L-1,FT47.8pmol·L-1,TSH237μIU·mL-1。甲状腺B超示甲状腺弥漫性病变。确诊为甲状腺功能减低,遂加用口服左甲状腺素钠片治疗。停非诺贝特3d后患者症状消失,27d后血CK、转氨酶基本恢复。     

国产与进口非诺贝特胶囊人体生物等效性研究

目的:研究国产与进口非诺贝特胶囊的人体生物等效性。方法:18名健康受试者采用双周期自身交叉试验,单剂量口服国产(受试制剂)与进口(参比制剂)非诺贝特胶囊200mg,以高效液相色谱法测定血浆中非诺贝酸的浓度,药-时数据经BECS生物利用度和等效性统计软件处理,计算主要药动学参数,并评价二者的生物等效性。结果:国产与进口非诺贝特胶囊的主要药动学参数分别为:t1/(221.34±3.31)、(21.83±4.35)h,Cma(x7.31±2.65)、(7.28±2.66)mg·L-1,tma(x4.72±0.57)、(4.67±0.59)h,AUC0～7(2170.09±54.06)、(172.2±54.64)mg·h·L-1,AUC0～∞(188.56±55.27)、(192.27±56.62)mg·h·L-1。国产非诺贝特胶囊的相对生物利用度F0～72为(98.87±6.76)%,F0～∞为(98.00±6.72)%。tmax采用非参数检验,Cmax、AUC0～72经对数转换后用方差分析和双单侧t检验,2种制剂的结果差异均无统计学意义。受试制剂AUC0～72和Cmax的90%可信限分别落在参比制剂的83.3%～116.9%和81.1%～124.4%范围内。结论:2种制剂生物等效。     

Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: A clinical update

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management.While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This ‘residual risk’ is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy.Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed.     

氟伐他汀联合非诺贝特治疗糖尿病合并高血脂的效果分析

目的分析非诺贝特联合氟伐他汀治疗的糖尿病合并高血脂患者的临床效果。方法 96例合并患有高血脂的糖尿病患者,采取随机数字表法将其分为对照组和观察组,各48例。对照组患者采用氟伐他汀治疗;观察组患者采用非诺贝特联合氟伐他汀治疗。观察两组治疗效果。结果对照组患者治疗总有效率为72.9%;观察组患者治疗总有效率为91.7%。两组治疗效果比较差异有统计学意义(P<0.05)。对照组和观察组患者治疗前后空腹血糖(FPG)水平与2hPG水平比较组内差异有统计学意义(P<0.05);且两组患者血糖水平治疗后组间差异有统计学意义(P<0.05)。对照组及观察组患者治疗前后TG、TC、HDL-C、LDL-C水平组内差异均有统计学意义(均P<0.05)。两组血脂指标治疗后组间差异均有统计学意义(P<0.05)。结论应用非诺贝特与氟伐他汀联合对合并患有高血脂的糖尿病患者进行治疗的临床效果非常明显。     

阿托伐他汀联合非诺贝特治疗急性冠脉综合征的临床效果分析

目的：对阿托伐他汀联合非诺贝特治疗急性冠脉综合征（acute coronary syndrome,ACS）的临床效果进行研究分析。方法：选取本院2010年8月-2012年8月间收治的ACS患者38例,按照随机数字表法分成对照组和试验组,每组19例。其中,对照组采取常规治疗并加用阿托伐他汀,试验组在对照组的基础上再加用非诺贝特进行联合治疗,比较两组患者治疗效果及不良反应。结果：治疗后,两组患者的低密度脂蛋白、胆固醇、三酰甘油、高密度脂蛋白等指标均优于治疗前,差异均有统计学意义（P〈0.05）;而试验组患者用药效果是明显优于对照组,两组比较差异有统计学意义（P〈0.05）。随访6个月心血管事件发生率明显降低,均无严重不良反应;试验组患者治疗后胸痛发作频率及持续时间与对照组相比也明显更低,两组比较差异有统计学意义（P〈0.05）。结论：阿托伐他汀与非诺贝特联合应用治疗ACS,能够产生非常好的协同增效作用,可以在临床上加以推广使用。     

Management of Hypertension and Dyslipidaemia in Patients Presenting with Hyperuricaemia: Case Histories

Summary

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipidlowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipidlowering drug (fenofibrate) with an additional hypouricaemic effect.     

非诺贝特联合氯沙坦钾氢氯噻嗪治疗舒张期高血压合并高甘油三酯血症60例体会

目的探讨单纯性舒张期高血压合并高甘油三酯血症的治疗方法。方法本研究通过随机、对照的方法,观察非诺贝特在降压治疗的基础上改善血脂异常对单纯舒张期高血压合并高甘油三酯血症患者舒张压的影响。结果经8周治疗发现,治疗组舒张压、三酰甘油下降幅度均大于对照组（P〈0．05）。结论非诺贝特与氯沙坦钾氢氯噻嗪联合用药治疗难治性舒张期高血压合并高甘油三酯血症具有更好的调脂、协同降压作用。     

代谢综合征与血清炎症因子的相关性研究

目的 观察非诺贝特对代谢综合征（MS）患者血清炎症因子的影响.方法入选20例MS患者,每天口服非诺贝特胶囊200mg,干预12周,干预前后采用氧化酶法测定血糖,酶法测定血脂,放免法测定胰岛素,ELISA法测定血清C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）及白介素-18（IL-18）.20名健康体检者作为正常对照组.结果 MS组患者血清CRP（2.70±0.59 vs.1.26±0.23,P〈0.01）、TNF-α（17.34±4.46 vs.11.43±2.49,P〈0.01）及IL-18（308.61±52.53vs.230.60±29.15,P〈0.01）等炎症因子较健康组明显升高.干预后,CRP（2.70±0.59 vs.2.40±0.34,P〈0.01）、TNF-α（17.34±4.46 vs.13.74±3.09,P〈0.01）及IL-18（308.61±52.53 vs.291.19±30.54,P〈0.05）水平均显著下降.结论 非诺贝特能够显著降低MS患者血清炎症因子水平.