Ramjattan Brian R, Callaghan Denis J G, Theiss Uwe
First Line Medical Services Ltd, Saint John 's, Newfoundland, Canada.
Clin Ther. 2002 Jul;24(7):1105-16. doi: 10.1016/s0149-2918(02)80022-4.
Newer fibrates such as micronized fenofibrate lower triglyceride (TG) levels, raise high-density lipoprotein cholesterol (HDL-C) levels, and lower fibrinogen levels, in addition to markedly lowering levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). A new microcoated "suprabioavailable" formulation of fenofibrate has demonstrated a superior pharmacokinetic profile compared with micronized fenofibrate 200 mg/d and may effectively reduce cardiovascular risk factors at the lower dose of 160 mg/d.
The goal of this study was to assess the efficacy and tolerability of the suprabioavailable" formulation of fenofibrate in patients with type IIa, type IIb, or type IV dyslipidemia.
This was a pooled analysis of data from 2 unpublished multicenter, open-label trials with a common protocol. After a 4-week washout period, patients with dyslipidemias not corrected by diet alone were assigned to receive microcoated fenofibrate 160 mg/d for 12 weeks. Changes in lipid profiles and safety variables (vital signs, body weight, and laboratory measures) were monitored throughout the study, and adverse events occurring between visits 1 and 5 were recorded by the study investigators.
The 2 trials included 375 men and women (mean age, 55.2 years) with type IIa (n = 158), type IIb (n = 195), type IV (n = 21), or other (n = 1) dyslipidemias. At end point. HDL-C levels in patients with type IIa, IIb, or IV dyslipidemia were increased by a respective 10.9% (P < 0.001), 16.1% (P < 0.001), and 12.1% (P < 0.05), whereas TG levels were decreased by a respective 27.7% (P < 0.001), 46.4% (P < 0.001), and 40.2% (P < 0.05). In patients with type IIa or IIb dyslipidemia, TC decreased (-14.3% in each group), LDL-C decreased (-20.6% and -13.2%, respectively), and the LDL-C/HDL-C ratio decreased (-26.7% and -22.0%) (all, P < 0.001). Overall, 121 of 375 (32.3%) patients experienced > or = adverse event (AE) (202 nonserious, 8 serious). Of these, 10.1% were judged to be possibly drug related. The most common nonserious AEs were those affecting the body as a whole (2.7% of patients) and the digestive system (5.3% of patients). No serious AE was considered drug related.
The new "suprabioavailable" microcoated, micronized formulation of fenofibrate appears to maintain the good efficacy and safety profile of micronized fenofibrate. In the study population with moderate dyslipidemia (types IIa and IIb), it promoted beneficial changes in major lipid risk factors for cardiovascular disease.
新型贝特类药物如微粒化非诺贝特除了能显著降低总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平外，还能降低甘油三酯（TG）水平、升高高密度脂蛋白胆固醇（HDL-C）水平以及降低纤维蛋白原水平。一种新的微包衣“超生物利用度”非诺贝特制剂与200mg/d微粒化非诺贝特相比，已显示出更优的药代动力学特征，并且在160mg/d的较低剂量下可能有效降低心血管危险因素。
本研究的目的是评估超生物利用度非诺贝特制剂在IIa型、IIb型或IV型血脂异常患者中的疗效和耐受性。
这是一项对2项未发表的多中心、开放标签试验数据进行的汇总分析，这2项试验采用相同方案。在4周的洗脱期后，将仅通过饮食无法纠正血脂异常的患者分配接受160mg/d微包衣非诺贝特治疗12周。在整个研究过程中监测血脂谱和安全变量（生命体征、体重和实验室指标）的变化，研究调查人员记录第1次和第5次访视之间发生的不良事件。
这2项试验纳入了375名患有IIa型（n = 158）、IIb型（n = 195）、IV型（n = 21）或其他（n = 1）血脂异常的男性和女性（平均年龄55.2岁）。在终点时，IIa型、IIb型或IV型血脂异常患者的HDL-C水平分别升高了10.9%（P < 0.001）、16.1%（P < 0.001）和12.1%（P < 0.05），而TG水平分别降低了27.7%（P < 0.001）、46.4%（P < 0.001）和40.2%（P < 0.05）。在IIa型或IIb型血脂异常患者中，TC降低（每组均为-14.3%），LDL-C降低（分别为-20.6%和-13.2%）以及LDL-C/HDL-C比值降低（-26.7%和-22.0%）（均P < 0.001）。总体而言，375名患者中有121名（32.3%）经历了≥1次不良事件（AE）（202次非严重事件，8次严重事件）。其中，10.1%被判定可能与药物有关。最常见的非严重AE是影响全身的事件（占患者的2.7%）和消化系统事件（占患者的5.3%）。没有严重AE被认为与药物有关。
新的“超生物利用度”微包衣、微粒化非诺贝特制剂似乎保持了微粒化非诺贝特良好的疗效和安全性。在中度血脂异常（IIa型和IIb型）的研究人群中，它促进了心血管疾病主要血脂危险因素的有益变化。
