衣折麦布/瑞舒伐他汀联用与双倍剂量瑞舒伐他汀治疗冠心病血脂异常患者的临床效果观察

目的：比较衣折麦布/瑞舒伐他汀与双倍剂量瑞舒伐他汀对冠心病血脂异常患者的疗效。方法：以2012年6月-2013年12月在我院接受治疗的110例冠心病血脂异常患者为研究对象,按照治疗方式的不同,随机分为两组,即衣折麦布/瑞舒伐他汀(10 mg/d+10 mg/d)联合治疗组(E/R组)与双倍剂量瑞舒伐他汀(20 mg/d)治疗组(D/R组),每组各55例比较两组患者服药12周的治疗效果。结果：与治疗前相比,E/R组患者总胆固醇(total cholesterol,TC)、三酰甘油及低密度脂蛋白胆固醇水平均显著降低(P<0.05),并且显著低于D/R组患者(P<0.05),而高密度脂蛋白胆固醇水平显著升高(P<0.05)。与治疗前相比,虽然E/R组7-烯胆烷醇/TC校正值显著升高(P<0.05),但是菜油固醇/TC的校正值显著降低(P<0.05),且后者的降低幅度1.35±0.70远大于前者0.41±0.21。同时,虽然D/R组7-烯胆烷醇/TC校正值显著降低(P<0.05),但是菜油固醇/TC的校正值显著升高(P<0.05),且前者的降低幅度0.08±0.01远小于后者的升高幅度0.34±0.15。结论：与双倍剂量瑞舒伐他汀治疗相比,衣折麦布/瑞舒伐他汀联用调脂作用更佳、更稳定,且胆固醇吸收与合成标志物的测定比血浆胆固醇水平更能反映机体胆固醇的代谢状态。     

Pharmacokinetic Interaction Between Rosuvastatin and Metformin in Healthy Korean Male Volunteers: A Randomized,Open-label, 3-period,Crossover, Multiple-dose Study

Purpose

Rosuvastatin is indicated for hypercholesterolemia or dyslipidemia and metformin mainly for type 2 diabetes. These 2 drugs are frequently prescribed in combination due to the high comorbidity of the 2 diseases. However the nature of pharmacokinetic interaction between the 2 drugs has not been previously investigated. The purpose of our study was to investigate the pharmacokinetic interaction between rosuvastatin and metformin in healthy Korean male volunteers.

Methods

This was a randomized, open-label, 6-sequence, 3-period, crossover, multiple-dose study. Eligible subjects, aged 20 to 50 years and within 20% of the ideal body weight, received 1 of the following 3 treatments for each period once daily for 5 consecutive days with a 10-day washout period between the treatments: monoadministration of rosuvastatin 10 mg tablet, monoadministration of metformin 750 mg tablet, and coadministration of rosuvastatin 10 mg tablet with metformin 750 mg tablet. Blood samples were collected up to 72 hours after the last dose and pharmacokinetic parameters for rosuvastatin and metformin were compared between combination and monotherapy. Adverse events were investigated and evaluated based on subject interviews and physical examinations.

Findings

Among the 36 enrolled subjects, 31 completed the study. The coadministration of rosuvastatin with metformin produced a significant pharmacokinetic interaction in rosuvastatin C_ss,max, with the 90% CI for the geometric mean ratio (coadministration:monoadministration) being 110.27% to 136.39% (P = 0.0029), whereas no significant interaction was observed in rosuvastatin AUC_tau, yielding the 90% CI of 104.41% to 118.95%. When metformin was coadministered with rosuvastatin, no significant pharmacokinetic interaction was observed for C_ss,max and AUC_tau of metformin, yielding the 90% CIs of the geometric mean ratio for coadministration to monoadministration as 87.38% to 102.54% and 86.70% to 99.08%, respectively. Overall, 19 mild and 1 moderate adverse events occurred in 12 subjects, with no significant differences in the incidence among the 3 treatments.

Implications

Although the C_ss,max of rosuvastatin was significantly influenced by coadministration with metformin, the degree of interaction seen was considered clinically insignificant, with no significant interaction observed in the other pharmacokinetic measures between the 2 drugs. These results imply that drug effects of rosuvastatin and metformin will also not be significantly influenced by coadministration of the 2 drugs. All treatments were well tolerated and no serious adverse events occurred. ClinicalTrials.gov identifier: NCT01526317.     

瑞舒伐他汀钙治疗高脂血症的临床研究

目的观察瑞舒伐他汀钙治疗高脂血症的安全性和有效性。方法将入选的48例高脂血症患者经4周停用降血脂药物处理后,采用随机、双盲、阳性药物平行对照方法分为3组,瑞舒伐他汀钙低剂量组（A1组）15例服用瑞舒伐他汀钙5mg／d;瑞舒伐他汀钙高剂量组（A2组）16例服用瑞舒伐他汀钙10mg／d;阿托伐他汀钙组（B组）15例服用阿托伐他汀钙10mg／d,服药时间为8周。分别于治疗前、治疗4周及8周末检测血清低密度脂蛋白胆固醇（LDI,-c）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDI,-C）变化,并记录血常规尿常规、心电图、血生化检测结果及不良反应发生情况。结果治疗前,3组年龄、性别、体重、收缩压、舒张压、心率以及血脂水平比较差异均无统计学意义（P〉0．05）;与治疗前相比,治疗4周和8周末,3组LDI,-C与TC均下降,差异有统计学意义（P〈0．05）。8周末,B组LDI,-C的降低值小于A1组和A2组差异有统计学意义（P〈0．05）,且A1组和A2组降低值差异均无统计学意义（P〉0．05）。血脂达标率中,B组低于A1组和A2组,差异有统计学意义（P〈0．05）。结论临床使用瑞舒伐他汀钙每日5mg～10mg治疗高胆固醇血症,能有效降低LDL-C水平,效果确切、安全。     

Rosuvastatin: a new inhibitor of HMG-CoA reductase for the treatment of dyslipidemia

Rosuvastatin (Crestor^®, AstraZeneca) is a synthetic statin that represents an advance on the pharmacologic and clinical properties of other agents in this class. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. Rosuvastatin is relatively hydrophilic and is selectively taken up by, and active in, hepatic cells. Rosuvastatin has the longest terminal half-life of the statins and is only minimally metabolized by the cytochrome P450 (CYP 450) enzyme system with no significant involvement of the 3A4 enzyme. Consistent with this finding is the absence of clinically significant drug interactions between rosuvastatin and other drugs known to inhibit CYP 450 enzymes. In patients with hypercholesterolemia, rosuvastatin 10–40 mg has been shown to reduce low-density lipoprotein cholesterol (LDL-C) levels by 52–63%, as well as increase high-density lipoprotein cholesterol (HDL-C) levels by up to 14% and reduce triglycerides (TG) by up to 28%. Studies have shown that rosuvastatin is superior to atorvastatin, simvastatin and pravastatin in reducing LDL-C and favorably modifying other components of the atherogenic lipid profile. The significant decreases in LDL-C with rosuvastatin treatment should help to improve attainment of lipid goals and reduce the requirement for dose titration. In addition, the effects of rosuvastatin on HDL-C and TG levels will be of benefit in treating patients with abnormalities such as mixed dyslipidemia and the metabolic syndrome. Rosuvastatin is well tolerated, with a safety profile comparable with that of other currently available statins.     

Pharmacologic strategies for the prevention of atherosclerotic plaque progression

Despite improved treatment options, coronary artery disease remains the leading cause of death in men and women in industrialized societies. Reduction of atherosclerotic disease will require the development and evaluation of new classes of pharmacologic agents capable of modifying the development and progression of the atherosclerotic disease process. The direct observation of coronary plaque burden and morphology with in vivo imaging modalities has been evaluated as an end point in serial pharmacologic intervention trials. This review will describe the use of intravascular ultrasound for such studies, summarize results from recent trials and outline potential future pharmacologic targets.     

瑞舒伐他汀对晚期内皮祖细胞增生、迁移及凋亡的影响

目的观察不同浓度及不同时间的瑞舒伐他汀(rosuvastatin)对晚期内皮祖细胞(endothelial progenitor cells,EPCs)增生(proliferation)、迁移(migration)和凋亡(apoptosis)的影响。方法采用密度梯度法从大鼠骨髓获取单个核细胞,培养28 d,通过FITC-UEA-I和DiI-acLDL双染色鉴定为正分化晚期EPCs。以不同浓度的瑞舒伐他汀(0.001、0.01、0.1、1.0、10、100μmol/L)和晚期EPCs共培养24 h,分别采用MTT比色法、Transwell小室及Tunel法检测其增生、迁移及凋亡功能;以浓度为0.1μmol/L的瑞舒伐他汀与晚期EPCs分别共培养1、3、6、12、24、48 h,应用同样方法检测其增生、迁移及凋亡功能。结果体外培养7 d时,细胞呈典型长梭形;28 d时,呈铺路石样,并可摄取FITC-UEA-I和DiI-acLDL。不同浓度的瑞舒伐他汀组与对照组相比均可明显地改善晚期EPCs的增生(P<0.05)、迁移(P<0.05)及凋亡(P<0.05)功能,且浓度为0.1μmol/L的瑞舒伐他汀改善细胞功能最强(P<0.05)。当瑞舒伐他汀浓度为0.1μmol/L、共培养不同时间后,与对照组相比可增强晚期EPCs的增生(P<0.05)、迁移(P<0.05)及抗凋亡(P<0.05)功能。结论瑞舒伐他汀能够提高晚期内皮祖细胞的增生、迁移功能,减少细胞的凋亡,且呈浓度及时间依赖性。     

不同用法瑞舒伐他汀降脂治疗急性冠脉综合征疗效观察

目的观察不同用法的瑞舒伐他汀降脂治疗急性冠脉综合征(ACS)疗效及安全性。方法选择158例ACS合并高脂血症患者。随机分为4组:A组(38例)予瑞舒伐他汀钙片10 mg,1次/d;B组(40例)予瑞舒伐他汀钙片10 mg,1次/d,阿昔莫司胶囊250 mg,3次/d;C组(40例)予瑞舒伐他汀钙片20 mg,1次/d;D组(40例)予瑞舒伐他汀钙片20 mg,1次/d,阿昔莫司胶囊250 mg,3次/d,4组患者疗程均为12周。观察治疗后血脂水平、血脂达标率、超敏C反应蛋白(hsCRP)、不良反应及心血管不良事件(MACE)的发生率。结果治疗后B、D组降脂疗效优于A、C组,有显著性差异;虽然D组血脂达标率及降低总胆固醇(TC)水平优于B组,但不良反应明显增加。结论瑞舒伐他汀联(10 mg,3次/d)合阿昔莫司(250 mg,3次/d)能有效地降低血脂水平,提高血脂达标率,降低hsCRP水平和MACE发生率,且不良反应较少,值得临床推广应用。     

瑞舒伐他汀钙对家兔腹主动脉球囊损伤后内膜增生及转化生长因子β1表达的影响

目的 观察瑞舒伐他汀钙对家兔腹主动脉球囊损伤内膜增生及转化生长因子β1(TGF-β1)表达的影响,并探讨其在防治支架术后再狭窄中的可能性及机制.方法 雄性新西兰兔20只,制作腹主动脉球囊损伤模型后随机分成他汀组与对照组(n=10).两组均予阿司匹林25mg/d、氯吡格雷25mg/d,他汀组加用瑞舒伐他汀钙1mg/(kg...     

瑞舒伐他汀对兔动脉粥样硬化的影响

目的观察瑞舒伐他汀对兔动脉粥样硬化的影响。方法新西兰大白兔30只,随机分为对照组、模型组与治疗组,每组10只。对照组以标准基础饲料喂养。模型组和治疗组以高脂饲料喂养4周后,行颈动脉内膜球囊损伤术,分别继续给予高脂饲料及高脂饲料加瑞舒伐他汀喂养6周。于4、10周末取血测定血脂及脂蛋白相关磷脂酶A2（Lp-PLA2）的水平。于10周末将兔处死时,取颈动脉标本行病理切片,免疫组织化学方法检测Lp-PLA2的表达。结果与对照组相比,模型组及治疗组血脂及Lp-PLA2水平均明显升高（t=2.11~218.85,P〈0.05）;治疗组血脂及Lp-PLA2水平均明显低于模型组（t=5.37~228.83,P〈0.05）。对照组未见动脉粥样硬化病变及Lp-PLA2表达,治疗组动脉粥样硬化斑块中Lp-PLA2的表达也明显低于模型组（t=4.71,P〈0.05）。结论瑞舒伐他汀可降低血脂及Lp-PLA2的水平,可能具有抗炎及抑制动脉粥样硬化进展的作用。     

A comparative evaluation of safety and efficacy of rosuvastatin, simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia

AIM:

To evaluate and compare the safety and efficacy of rosuvastatin, simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia.

MATERIALS AND METHODS:

This open-label, randomized, parallel group, comparative, prospective study of 12-weeks duration included 60 patients of type-2 diabetes with dyslipidemia having good glycemic control with fixed dose combination of tablet glimepiride + metformin and divided into three groups of twenty each. Group-1 patients have received tablet rosuvastatin 10 mg once daily, group-2 received tablet atorvastatin 10 mg once daily, and group-3 received tablet simvastatin 10 mg once daily for 12 weeks each. The levels of serum cholesterol, serum triglyceride, LDL, VLDL, and HDL were assessed at baseline and at the end of 12 weeks.

RESULTS:

The mean serum cholesterol, serum triglyceride, LDLc, and VLDLc levels were significantly reduced on therapy (P<0.001). Simultaneously, the mean levels of HDL were highly significantly increased (P<0.001) after therapy for 12 weeks with rosuvastatin, atorvastatin, and simvastatin. Reduction of LDL levels in rosuvastatin group was statistically significant when compared with those of simvastatin group (P< 0.05) but was statistically nonsignificant when compared with atorvastatin group (P> 0.05). Conclusion: 10 mg of rosuvastatin was comparable to 10 mg of atorvastatin and more efficacious than 10 mg simvastatin in reducing LDL levels after 12 weeks of therapy in patients of type 2 diabetes mellitus with dyslipidemia.