The Protective Effect of Rosuvastatin on Ischemic-Brain Injury and Its Mechanism

The statins, which lower plasma cholesterol levels, are 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors. To date, stains have developed to third generation, which include five commonly used stains: lovastatin, pravastatin, simvastatin, fluvastatin and atorvastatin. Recently, a new statin, named rosuvas-tatin, was used in the third stage of clinical trial. Rosu-vastatin, in contrast to most other statins, has the more powerful capability to lower plasma cholesterol levels,…     

处方工艺对瑞舒伐他汀钙片混合均匀度及含量均匀度的影响

目的 研究处方中的辅料及工艺对瑞舒伐他汀钙片混合均匀度及含量均匀度的影响。方法 采用粉末直接压片工艺，通过单因素试验，考察处方中乳糖的型号、微晶纤维素的型号、乳糖与微晶纤维素的比例、钙盐的种类及交联聚维酮用量对混合均匀度及含量均匀度的影响；同时研究混合工艺对混合均匀度及压片工艺对含量均匀度的影响。结果 不同的乳糖型号（T80、PW80、315）、微晶纤维素型号（PH102、M102、102）、乳糖与微晶纤维素的比例（1:1、3:1、1:3）、钙盐的种类（磷酸钙（细颗粒）、无水磷酸氢钙（细颗粒、细粉）、碳酸钙（细粉））的处方混合均匀度及含量均匀度良好，磷酸钙（粗颗粒）的处方混合均匀度及含量均匀度较差。在混合容器中加入50%的乳糖，之后加入原料药、微晶纤维素、交联聚维酮和磷酸钙，以10 r·min-1混合20~25 min；再加入剩余的乳糖，以10 r·min-1混合15~25 min，物料混合均匀度良好。重力加料器及压片速度（10~20 r·min-1）的含量均匀度良好；强制加料器及压片速度（30 r·min-1）的含量均匀度较差。结论：通过研究筛选出了适合粉末直压工艺的乳糖型号、微晶纤维素型号、乳糖与微晶纤维素比例、钙盐种类及交联聚维酮用量。考察了混合工艺参数范围，优选了重力加料器及压片速度（10~20 r·min-1），获得了良好的混合均匀度和含量均匀度。     

Do Statins Counteract the Effect of Antidiabetic Drugs? Results of the SCEAD Study

PurposeDiabetes and dyslipidemia are leading causes of mortality and morbidity. According to international guidelines, statins are the cornerstone of treatment in patients with diabetes and/or dyslipidemia. However, statins and antidiabetic agents have opposite pharmacological effects, because statins, particularly atorvastatin and rosuvastatin, impair glucose homeostasis, increasing the risk of new-onset diabetes, whereas antidiabetic drugs improve glycemic homeostasis. The aim of this study was to investigate the effect of atorvastatin, rosuvastatin, and pitavastatin on glucose homeostasis in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia during stable treatment with hypoglycemic drugs.Materials and MethodsThe study was conducted as a pilot, prospective, randomized, open label, parallel group with blinded-endpoints (PROBE) study. Of 180 recruited patients with T2DM and dyslipidemia, 131 were randomized to atorvastatin (n=44), rosuvastatin (n=45), and pitavastatin (n=42) and treated for 6 months.ResultsFasting plasma glucose (FPG) marginally decreased in patients assigned to atorvastatin (-3.5 mg/dL, p=0.42) and rosuvastatin (-6.5 mg/dL, p=0.17), while it decreased much more in patients treated with pitavastatin (-19.0 mg/dL, p<0.001). Mean glycated hemoglobin A1c (HbA1c ) values remained unchanged during treatment with atorvastatin (-0.10%, p=0.53) and rosuvastatin (0.20%, p=0.40), but were significantly reduced with pitavastatin (-0.75%, p=0.01). Atorvastatin, rosuvastatin, and pitavastatin significantly lowered (p<0.001) plasma levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides, while high-density lipoprotein-cholesterol (HDL-C) levels increased significantly (p=0.04) only in the pitavastatin group.ConclusionThe results of the present study suggest that pitavastatin affects FPG and HbA1c less than atorvastatin and rosuvastatin in patients with T2DM and concomitant dyslipidemia. Lipid-lowering efficacies were not significantly different among the three statins, with the exception of HDL-C, which increased significantly with pitavastatin. Although the pharmacological mechanism of pitavastatin on glucose homeostasis in patients with T2DM during stable antidiabetic therapy is not known, it can be assumed that pitavastatin has less drug interaction with hypoglycemic agents or that it increases plasma levels of adiponectin.     

Significant decrease in plasmad‐dimer levels and mean platelet volume after a 3‐month treatment with rosuvastatin in patients with venous thromboembolism

BackgroundInflammation has been considered as a possible mechanism for the initiation and recurrence of venous thromboembolism (VTE). Statins have anti‐inflammatory and potential immune‐modulatory effects, but their effect on plasmad‐dimer levels is controversial.HypothesisIn this study, we aimed to evaluate the impact of rosuvastatin on D‐dimer and other inflammatory serum markers in VTE patients.MethodsWe conducted a prospective, randomized study on 228 patients with VTE. Control group received conventional treatment (warfarin or rivaroxaban), whereas rosuvastatin‐intervention group received rosuvastatin 10 mg daily, in addition to their conventional treatment for 3 months. Serum markers were extracted from both groups at the baseline and 3 months after the beginning of treatment.ResultsAfter 3 months, in patients of the intervention group, there was a statistically significant decrease in levels ofd‐dimer and mean platelet volume (MPV) but no significant change in neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio.ConclusionsOur results showed that a 3‐month treatment with 10 mg rosuvastatin daily can significantly decrease the plasma levels ofd‐dimer and MPV, which would support a potential role of statins to reduce activated systemic inflammation among VTE patients. Such effects can be used to reduce the rate of recurrent VTE in these patients.     

Predicting the oral absorption of a poorly soluble,poorly permeable weak base using biorelevant dissolution and transfer model tests coupled with a physiologically based pharmacokinetic model

通过构建瑞舒伐他汀空腹状态下的生理药动学(physiologically based pharmacokinetic model,PBPK)模型,预测其餐后状态下的吸收,并探究其可能的食物效应机制,为服用他汀类药物的高脂血症患者提出合理的饮食建议,提高BCSⅢ类他汀类药物的药物吸收。

根据文献和已有研究获得瑞舒伐他汀建模的理化参数、生物药剂学参数以及药动学参数,利用GastroPlus^TM软件建立瑞舒伐他汀餐后给药的PBPK预测模型,并结合实测的血药浓度数据验证模型,判断是否可以准确预测出瑞舒伐他汀餐后的药物吸收结果,并进行参数敏感性分析。

通过构建瑞舒伐他汀PBPK模型预测其餐后吸收,计算得到模型预测数据与实测数据的平均折叠误差和绝对平均折叠误差<2,结合模型验证的拟合相关系数表明拟合效果较好,同时参数敏感性分析提示高热量饮食、药物的油水分配系数(LogD)和渗透性对瑞舒伐他汀的吸收影响较大。

所建立的模型能够较好地预测瑞舒伐他汀餐后状态下的吸收,基于参数敏感性分析结果,为服用BCSⅢ类他汀类药物的高脂血症患者提出合理的饮食建议,包括适当增加饮食中蛋白质的比重、减少脂肪和水溶性膳食纤维的占比等,可提高BCSⅢ类他汀类药物的肠道吸收。

     

脉血康胶囊联合瑞舒伐他汀对冠脉临界病变患者冠脉病变程度的影响

目的研究脉血康胶囊联合瑞舒伐他汀对冠脉临界病变患者钙库操纵性钙通道蛋白(SOCC)基质交联分子1(STIM1)、钙释放激活钙通道蛋白Orai1及瞬时受体电位通道1(TRPC1)蛋白水平和冠脉病变严重程度的影响。方法将2015年1月—2016年12月北京安贞医院经定量冠脉造影检查确诊冠脉临界病变(BCL)住院患者160例设为临界病变组(BCL组),150例无冠脉病变的受试者为对照组(简称CTR组)。BCL组随机分为常规治疗组(简称RTT组,80例)和联合治疗组(简称CBT组,80例)。RTT组给予生活方式改善、阿司匹林、AECI、β受体阻滞剂及瑞舒伐他汀10 mg等药物。CBT组在常规药物治疗基础上,每日加用瑞舒伐他汀15 mg和脉血康胶囊3.0 g,连续治疗12个月。检测血小板STIM1、Orai1、TRPC1、高敏C-反应蛋白(hs-CRP)水平及TC、LDL-C、HDL-C、TG浓度。评价BCL组平均狭窄程度(MPS)。结果BCL组130例受试者复查冠脉造影。与本组治疗前比较,治疗后CBT组和RTT组血小板STIM1、Orai1、TRPC1水平均降低(P<0.05);CBT组冠脉临界病变的MPS明显减低(59.74±9.72vs.38.92±13.84,P<0.05),RTT组MPS有所下降(58.96±8.67vs.55.43±10.03),但差异无统计学意义(P>0.05)。与RTT组比较,治疗后CBT组血小板STIM1、Orai1、TRPC1、TC、LDL-C、TG、和hs-CRP明显降低(P<0.05,P<0.01),且CBT组MPS差值大于RTT组(P<0.01)。结论脉血康胶囊3.0 g和瑞舒伐他汀15 mg每日联合应用可降低SOCC水平,其可能是冠脉临界病变治疗的优化选择。     

心脑舒通片联合瑞舒伐他汀治疗脑梗死伴发抑郁症60例

目的：观察心脑舒通片联合瑞舒伐他汀治疗脑梗死伴发抑郁症的临床疗效。方法：将120例脑梗死伴发抑郁症患者随机分为治疗组与对照组各60例,两组都给予盐酸氟西汀和瑞舒伐他汀对症治疗,在此基础上治疗组加用心脑舒通片治疗,治疗周期为1个月。结果：治疗组与对照组的有效率分别为75．0％和50．0％,治疗组有效率明显高于对照组（P〈0．05）。两组治疗后HAMD与NIHSS评分均明显下降（P〈0．05）,组内与组间比较差异均有统计学意义（P〈0．05）。两组治疗后的血浆NO浓度均明显升高（P〈0．05）,组问比较差异有统计学意义（P〈0．05）。两组干预期间的不良反应发生率组间比较差异无统计学意义（P〉0．05）。结论：心脑舒通片联合瑞舒伐他汀治疗脑梗死伴发抑郁症疗效显著,安全性佳,其作用机制与提高血浆NO表达有关。     

瑞舒伐他汀对不稳定型心绞痛患者PCI术后心肌损伤的保护作用

目的探讨瑞舒伐他汀在不稳定型心绞痛（UAP）经皮冠状动脉介入（PCI）术中对心肌损伤的保护作用。方法94例经PCI治疗的UAP患者随机分为观察组（n=47）与对照组（n=47）,观察组在常规治疗基础上给予瑞舒伐他汀治疗,对照组在常规治疗基础上给予阿托伐他汀治疗,对比2组患者心肌损伤情况。结果2组患者术前肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）、人心型脂肪酸结合蛋白（h-FABP）以及超敏C反应蛋白（hs—CRP）及氧化亚氮（N0）比较差异均无统计学意义（P〉0．05）。术后2个月时,观察组上述5项指标均无显著改变（P〉0．05）;对照组CK-MB、cTnI、h-FABP及hs-cRP均显著高于术前（P〈0．01）,术后NO显著低于术前（P〈0．01）。结论瑞舒伐他汀对UAP患者PCI术后心肌损伤具有有效的保护作用,安全可靠,值得推广。     

Effect of 2-year treatment with low-dose rosuvastatin on intima-media thickness in hypercholesterolemic subjects with asymptomatic carotid artery disease

Objectives: Recent evidence indicates that rosuvastatin 40 mg may exert a beneficial effect in both carotid and coronary atherosclerosis progression. In particular, 2-year rosuvastatin treatment reduced the progression of carotid intima-media thickness (cIMT) in patients with low cardiovascular risk. However, despite the fact that in clinical practice lower doses of rosuvastatin are usually administered at this time, there are no clear data about its effect on cIMT. Thus, the aim of this study was to evaluate the effect of rosuvastatin 10 mg/day on cIMT over a 2-year follow-up.

Methods: Forty-five patients with hypercholesterolemia and asymptomatic carotid atherosclerosis on baseline carotid ultrasound investigation were treated with rosuvastatin 10 mg/day for 24 months. cIMT and lipid profile were assessed after 12 months and at the end of the study (24 months).

Results: After 24 months, the treatment showed a 35.67% reduction in low-density lipoprotein cholesterol concentration (171 vs 110 mg/dl; p < 0.001), a 32.27% reduction in total cholesterol (251 vs 170 mg/dl; p < 0.001), a 19.67% increase in high-density lipoprotein cholesterol concentration (49 vs 61 mg/dl; p < 0.001), and a 10% reduction in triglycerides (120 vs 108 mg/dl; p < 0.01). Rosuvastatin treatment was associated with a 26.6% reduction in left cIMT (1.20 vs 0.90 mm; p < 0.001) and a 22.2% reduction in right cIMT (1.22 vs 0.95 mm; p < 0.001).

Conclusion: Two-year treatment with rosuvastatin 10 mg/day in hypercholesterolemic adults with evidence of subclinical atherosclerosis establishes a significant reduction in cIMT and improves lipid and lipoprotein levels, with a good tolerability profile.