Meta-analysis of the comparative efficacy and safety of pitavastatin and atorvastatin in patients with dyslipidaemia

What is known and Objective: Pitavastatin is the latest available statin. It has been shown to be effective in the treatment of dyslipidaemia. This meta‐analysis was aimed at evaluating the effects of pitavastatin on lipid profiles in patients with dyslipidaemia compared with atorvastatin. Methods: Clinical trials were identified through electronic searches (MEDLINE, CINAHL, EBM review, and the Cochrane Library) up to January 2011 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (i) randomized controlled trials that evaluated pitavastatin at the recommended dose vs. atorvastatin in patients with dyslipidaemia, (ii) lasting at least 6 weeks, (iii) reporting total cholesterol (TC), LDL‐C, HDL‐C or triglyceride (TG) levels and (iv) published in English. Treatment effect was estimated with the mean difference in the per cent changes in lipid profiles from baseline to final assessment between pitavastatin and atorvastatin. Results: Seven trials involving 1529 patients were included. Pitavastatin reduced LDL‐C level as effectively as atorvastatin (mean difference 0.97%, 95% CI ?0.48% to 2.42%). The reductions in TC and TG levels were also comparable between the two drugs. The mean differences were 1.22% (95% CI ?0.55% to 2.99%) and 2.3% (95% CI ?1.06% to 5.65%), respectively. However, HDL‐C levels increased significantly more with pitavastatin than with atorvastatin (mean difference 1.78%, 95% CI 0.20–3.36%, P = 0.03). What is new and Conclusions: Pitavastatin was as effective as atorvastatin in lowering LDL‐C, TC and TG levels. Pitavastatin was marginally superior to atorvastatin in increasing HDL‐C levels.     

匹伐他汀治疗高胆固醇血症36例的临床疗效分析

目的 探讨匹伐他汀治疗高胆固醇血症的临床疗效.方法 将68例高胆固醇血症患者按盲目随机法分为两组,观察组36例使用匹伐他汀,对照组32例使用辛伐他汀.治疗结束后,将总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、高密度蛋白胆固醇(HDL-C)水平进行对比.结果 两组TC与LDL-C降低程度与治疗前相比均有明显差异(P＜0.05),TG与HDL-C均无明显差异(P＞0.05).两组患者LDL-C水平的达标率与不良反应发生率均无明显差异(P＞0.05).结论 匹伐他汀治疗高胆固醇血症疗效显著,能有效降低TC及LDL-C水平,不良反应率低,安全水平高,值得临床推广.     

LC-MS法测定人血浆匹伐他汀药物浓度及应用

  目的 建立液质联用(LC-MS直接沉淀法测定人血浆匹伐他汀的浓度。方法 Waters Cosmosil Packed Coulmn C₁₈-MS-Ⅱ(2.0 mm×150 mm, 5 μm色谱柱, 流动相为10 mmol·L^-1甲酸胺(含0.1%甲酸-乙腈(40∶60, 流速为0.3 mL·min^-1, 进样体积为20 μL, 柱温为40 ℃, 样品室温度为15 ℃,采用内标定量法,内标为罗素伐他汀。结果 匹伐他汀线性范围为0.5~1 000 ng·mL^-1, 最低检测限为0.1 ng·mL^-1, 方法灵敏、稳定、特异性高, 并已成功地应用到人血浆匹伐他汀药动学研究。 结论 该方法简便、准确、重复性好, 可以准确地定量人血浆匹伐他汀的浓度, 适于药理科研。     

乳酸-羟基乙酸共聚物包载匹伐他汀纳米粒的制备及其对内皮祖细胞的增殖作用

制备乳酸-羟基乙酸共聚物(PLGA)包载匹伐他汀纳米粒,检测其形貌、粒径、载药量、包封率及体外释药特点,研究其对内皮祖细胞的增殖作用。采用溶剂扩散法制备PLGA包载的匹伐他汀纳米粒,扫描电镜观察纳米粒形貌,激光粒度仪测定粒径,高效液相色谱法检测并计算载药量、包封率,体外药物释放实验检测纳米粒的缓释效能,CCK8法检测空白PLGA纳米粒及匹伐他汀纳米粒对内皮祖细胞的活性影响。扫描电镜下匹伐他汀纳米粒呈圆球形,平均粒径在(230.1±45)nm,载药量与包封率分别为(10.00±1.83)%、(35.54±5.40)%,具备缓释性能,不同浓度空白PLGA纳米粒对内皮祖细胞活性均无影响,匹伐他汀纳米粒组(0.01、0.1 μmol/L)可显著改善内皮祖细胞的增殖活性,与同浓度匹伐他汀原药组相比差异显著。结果表明,溶剂扩散法可制备形态较好的匹伐他汀纳米粒,具备缓释性能,载体材料具有较好的细胞生物相容性,匹伐他汀纳米粒显著改善内皮祖细胞增殖活性。     

HPLC-MS/MS法测定人血浆中匹伐他汀钙的浓度及应用

目的建立高效液相色谱-质谱（HPLC-MS/MS）法测定人血浆中匹伐他汀钙的浓度,评价2种匹伐他汀钙片在人体内的生物等效性。方法血浆中加入内标瑞舒伐他汀后,甲基叔丁基醚萃取,选用Venusil MP-C18（150 mm×2.1 mm,5μm,Agela）色谱柱,流动相为30 mmol·L-1乙酸铵（含0.1%甲酸）-甲醇（25：75）,流速0.4 mL·min-1,进样体积为20μL,柱温为40℃。以多重离子反应监测模式进行检测：m/z421.9→m/z290.1（匹伐他汀）,m/z482.2→m/z258.2（瑞舒伐他汀）。结果匹伐他汀钙的线性范围为0.110～56.0μg·L-1,本方法灵敏、稳定、特异性高,可应用于生物等效性研究。结论该方法重复性好,可以准确测量人血浆中匹伐他汀钙的浓度,适用于临床匹伐他汀的生物等效性研究。     

Pharmacokinetics of pitavastatin in subjects with Child-Pugh A and B cirrhosis

AIM: Lipid lowering therapy with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is increasingly used for the prevention of cardiovascular events, but they should be used with caution in patients with impaired liver function. We therefore studied the pharmacokinetics of pitavastatin in patients with liver cirrhosis. METHODS: Plasma concentrations of pitavastatin were determined after administration of 2 mg single-dose pitavastatin to 12 male patients with liver cirrhosis (six Child-Pugh grade A and six grade B). These results were compared with the single-dose pharmacokinetic results obtained from six male volunteers without liver disease. RESULTS: Administration of 2 mg single-dose pitavastatin to patients with Child-Pugh grade A and grade B cirrhosis resulted in a 1.19- and 2.47-fold increase in Cmax and 1.27- and 3.64-fold increase in AUCt, respectively, when compared with normal subjects. The geomean Cmax of pitavastatin was 59.5 ng ml(-1), 70.7 ng ml(-1) and 147.1 ng ml(-1) in the control, Child-Pugh grade A and Child-Pugh grade B groups, respectively. The geomean AUCt of pitavastatin in the three groups was 121.2 ng h(-1) ml(-1), 154.2 ng h(-1) ml(-1) and 441.7 ng h(-1) ml(-1), respectively. The geomean Cmax of pitavastatin lactone was 20.3 ng ml(-1), 19.1 ng ml(-1) and 9.9 ng ml(-1) in the control, Child-Pugh grade A and grade B groups, respectively. The AUCt of pitavastatin lactone was 120.2 h(-1) ml(-1), 108.8 h(-1) ml(-1) and 87.5 h(-1) ml(-1), respectively. CONCLUSION: The plasma concentration of pitavastatin is increased in patients with liver cirrhosis. In such patients, caution is required, although dose reduction may not be necessary in Child-Pugh A cirrhosis.     

降血脂新药匹伐他汀

匹伐他汀是新一代他汀类药物.该药不仅具有较强的HMG-CoA还原酶抑制作用,而且呈肝细胞选择性,药动学性质优异,安全性好,已被制药界誉为是"超级他汀".现就匹伐他汀的药理及临床应用进行综述.     

An evaluation of pitavastatin for the treatment of hypercholesterolemia

Introduction: Statins are the first line of therapy to reduce low-density lipoprotein cholesterol (LDL-C) in order to decrease cardiovascular events. Pitavastatin is the latest statin to be introduced to the market.

Areas covered: In this article, the authors review the efficacy, safety, and tolerability of pitavastatin. The authors also review a recent cardiovascular outcome study.

Expert opinion: Pitavastatin produces dose-dependent reductions in LDL-C at lower doses than other statins. The maximum approved dose of 4 mg reduces LDL-C by about 40–49% in different patient groups and is equivalent to atorvastatin 20 mg in this effect. Pitavastatin undergoes minimal metabolism so drug–drug interactions are less likely than with many other statins, but it can interact with some drugs that inhibit drug transporters. Compared with other statins, it has been associated with greater increases in high-density lipoprotein cholesterol and it was found to be less likely to cause new onset diabetes. In a recent study in Japanese patients with stable coronary artery disease, pitavastatin 4 mg was more effective than pitavastatin 1 mg in reducing cardiovascular events. Therefore, the highest dose may be preferred in high-risk patients.     

Pleiotropic effects of pitavastatin

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are established first line treatments for hypercholesterolaemia. In addition to the direct effects of statins in reducing concentrations of atherogenic low density lipoprotein cholesterol (LDL-C), several studies have indicated that the beneficial effects of statins may be due to some of their cholesterol-independent, multiple (pleiotropic) effects which may differ between different members of the class. Pitavastatin is a novel synthetic lipophilic statin that has a number of pharmacodynamic and pharmacokinetic properties distinct from those of other statins, which may underlie its potential pleiotropic benefits in reducing cardiovascular risk factors. This review examines the principal pleiotropic effects of pitavastatin on endothelial function, vascular inflammation, oxidative stress and thrombosis. The article is based on a systematic literature search carried out in December 2010, together with more recent relevant publications where appropriate. The available data from clinical trials and in vitro and animal studies suggest that pitavastatin is not only effective in reducing LDL-C and triglycerides, but also has a range of other effects. These include increasing high density lipoprotein cholesterol, decreasing markers of platelet activation, improving cardiac, renal and endothelial function, and reducing endothelial stress, lipoprotein oxidation and, ultimately, improving the signs and symptoms of atherosclerosis. It is concluded that the diverse pleiotropic actions of pitavastatin may contribute to reducing cardiovascular morbidity and mortality beyond that achieved through LDL-C reduction.