Stein E A
Medical Research Laboratories, Highland Heights, Kentucky 41076, USA.
Drugs. 1998;56 Suppl 1:25-31; discussion 33. doi: 10.2165/00003495-199856001-00004.
Cerivastatin is a third generation pure enantiomeric HMG-CoA reductase inhibitor. It reduces low density lipoprotein (LDL)-cholesterol by 22 to 44% at doses of 0.1 to 0.8 mg/day. The drug has been extensively evaluated for more than 5 years in clinical trials and is currently marketed in a number of countries at doses of 0.1 to 0.3 mg/day. Cerivastatin has been tested in more than 4000 patients during extensive phase II and III studies. About 40% of patients in these trials were women, and many participants were aged between 65 and 75 years. The trial populations had moderate to severe hypercholesterolaemia, with mean baseline LDL-cholesterol levels of approximately 5.2 mmol/L (200 mg/dl). In large phase III trials, cerivastatin, over the dosage range of 0.1 to 0.4 mg/day, reduced LDL-cholesterol by 22.4 to 36.1% from baseline. As with other HMG-CoA reductase inhibitors, the log-linear dose-response curve of cerivastatin showed a 6% additional decrease in mean LDL-cholesterol levels for each doubling of the daily dose, with no plateau effect noted at the highest dosage yet tested (0.8 mg/day). High density lipoprotein cholesterol levels increased by 4 to 10% during cerivastatin therapy. This effect, which was consistent with that of other HMG-CoA reductase inhibitors, was not dose related. As has been found with other statins, the triglyceride-lowering effects of cerivastatin are dependent on baseline triglyceride levels, with very small reductions occurring in patients with low initial levels [< 1.7 mmol/L (150 mg/dl)], and larger dose-dependent reductions of up to 36% with the 0.4 mg/day dose observed in patients with baseline triglyceride levels >2.8 mmol/L (250 mg/dl). Cerivastatin was well tolerated in all studies. Cerivastatin recipients and recipients of other HMG-CoA reductase inhibitors experienced a similar incidence of adverse events (including hepatic transaminase elevations) in comparative studies. Cerivastatin is an effective and safe lipid-lowering agent for most patients with hypercholesterolaemia.
西立伐他汀是第三代纯对映体HMG - CoA还原酶抑制剂。在每日剂量为0.1至0.8毫克时，它可使低密度脂蛋白（LDL）胆固醇降低22%至44%。该药物在临床试验中已经进行了超过5年的广泛评估，目前在多个国家以每日0.1至0.3毫克的剂量上市。在广泛的II期和III期研究中，西立伐他汀已在4000多名患者身上进行了测试。这些试验中约40%的患者为女性，许多参与者年龄在65至75岁之间。试验人群患有中度至重度高胆固醇血症，平均基线LDL胆固醇水平约为5.2毫摩尔/升（200毫克/分升）。在大型III期试验中，西立伐他汀在0.1至0.4毫克/天的剂量范围内，使LDL胆固醇较基线水平降低了22.4%至36.1%。与其他HMG - CoA还原酶抑制剂一样，西立伐他汀的对数线性剂量反应曲线显示，每日剂量每增加一倍，平均LDL胆固醇水平额外降低6%，在目前测试的最高剂量（0.8毫克/天）下未观察到平台效应。在西立伐他汀治疗期间，高密度脂蛋白胆固醇水平升高了4%至10%。这种效应与其他HMG - CoA还原酶抑制剂一致，与剂量无关。正如在其他他汀类药物中所发现的那样，西立伐他汀的降甘油三酯作用取决于基线甘油三酯水平，初始水平较低[<1.7毫摩尔/升（150毫克/分升）]的患者甘油三酯降低幅度很小，而基线甘油三酯水平>2.8毫摩尔/升（250毫克/分升）的患者在0.4毫克/天的剂量下观察到高达36%的剂量依赖性更大降幅。在所有研究中，西立伐他汀耐受性良好。在比较研究中，接受西立伐他汀的患者和接受其他HMG - CoA还原酶抑制剂的患者发生不良事件（包括肝转氨酶升高）的发生率相似。对于大多数高胆固醇血症患者来说，西立伐他汀是一种有效且安全的降脂药物。
