Simultaneous separation of antihyperlipidemic drugs by green ultrahigh-performance liquid chromatography–diode array detector method: Improving the health of liquid chromatography

Statins in combination with fibrates show beneficial effects on the lipoprotein profile of patients because they have positive complimentary effects on lipid profile. A new green ultrahigh-performance liquid chromatography–diode array detector method for simultaneous analysis of simvastatin (SMV) and fenofibrate (FNF) in standard form, marketed formulations, and self-emulsifying drug delivery system formulations was developed and validated in the present investigation. The method utilized C₁₈ as stationary phase and a combination of methanol:water (8:2) as an eluent. It was found that selected eluent provided short run time (2.5 minutes), better peak symmetry and satisfactory values of other chromatographic parameters such as resolution (Rs = 2.325), capacity factor (k, 3.0 and 4.2 for SMV and FNF, respectively), selectivity (α =1.4), and number of theoretical plates (N, 4265 and 5285 for SMV and FNF, respectively). An excellent linear relationship (r² 0.998 and 0.997 for SMV and FNF, respectively) was observed for linear regression data for the calibration plots. The developed system was validated for accuracy, precision, robustness (˃ 2% for both drugs) and recovery (98–102% for both drugs). Results obtained from the statistical treatment of the values obtained for different parameters proved that the method is suitable, reproducible, and selective for the simultaneous analysis of SMV and FNF in bulk, marketed, and self-emulsifying drug delivery system formulations. The replacement of commonly applied toxic solvents with innocuous and environmentally benign solvents provides a better option than the more toxic processes in drug analysis.     

Simvastatin induces osteogenic differentiation of murine embryonic stem cells

Statins are potent inhibitors of cholesterol synthesis. Several statins are available with different molecular and pharmacokinetic properties. Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin, allowing its passive diffusion through the cell membrane. In vitro studies on bone marrow stromal cells, osteoblast‐like cells, and embryonic stem cells have shown statins to have cholesterol‐independent anabolic effects on bone metabolism; alas, statins were supplemented in osteogenic medium, which does not facilitate elucidation of their potential osteoinductive properties. Embryonic stem cells (ESCs), derived from the inner cell mass of the blastocyst, are unique in that they enjoy perpetual self‐proliferation, are pluripotent, and are able to differentiate toward all the cellular lineages composing the body, including the osteogenic lineage. Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases, even though there are several hurdles that still need to be overcome. Herein we demonstrate, for the first time to our knowledge, that simvastatin induces murine ESC (mESC) differentiation toward the osteogenic lineage in the absence of osteoinductive supplements. Specifically, we found that a simvastatin concentration in the micromolar range and higher was toxic to the cells and that an effective concentration for osteoinduction is 0.1 nM, as shown by increased alizarin red staining as well as increased osteocalcin and osetrix gene expression. These results suggest that in the future, lipophilic simvastatin may provide a novel pharmacologic agent for bone tissue engineering applications. © 2010 American Society for Bone and Mineral Research.     

Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients

ABSTRACT

Objective: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.

Research design and methods: Double-blind, multicenter, 6‐week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10?mg/day), the next highest (10/40 or 20?mg/day), and maximum doses (10/80 or 40?mg/day).

Results: At all doses and across doses, ezetimibe/simvastatin reduced LDL‐C levels significantly more (52–61%) than rosuvastatin (46–57%; p ≤ 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p ≤ 0.005) attained LDL‐C levels < 70?mg/dL (1.8?mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (?p < 0.001), non-high-density lipoprotein cholesterol (?p < 0.001), lipid ratios (?p ≤ 0.003), and apolipoprotein B (?p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (?p = 0.004) and next highest (?p = 0.006) doses, and across all doses (?p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10?mg versus 10/20?mg/day (?p = 0.004) and 40?mg versus 10/80?mg/day (?p < 0.001).

Conclusion: Ezetimibe/simvastatin was more effective than rosuvastatin in LDL‐C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies.     

比索洛尔联合辛伐他汀对不稳定性心绞痛的治疗效果及应用优势探析

目的：探究比索洛尔联合辛伐他汀治疗不稳定性心绞痛的临床效果并分析其临床应用时的优势。方法：选取该院2015年9月至2016年1月收治的78例不稳定性心绞痛患者,将其随机分为实验组及对照组,每组39例,实验组患者在治疗时采用比索洛尔联合辛伐他汀治疗,对照组患者仅采用辛伐他汀治疗。3个月后观察并比较两组患者心绞痛的缓解情况和心电图的改善状况。结果：治疗3个月后,两组患者的心绞痛程度及心电图情况较治疗前均有明显改善,实验组改善程度比对照组改善程度更有优势,且比较差异具有统计学意义（P＜0.05）。结论：比索洛尔联合辛伐他汀治疗不稳定性心绞痛取得了令人满意的效果,值得在今后的临床治疗中应用及推广。     

辛伐他汀对血脂正常的老年冠心病患者颈动脉粥样硬化斑块的影响

目的观察不同剂量辛伐他汀对血脂正常水平的老年冠心病患者颈动脉粥样硬化斑块的消退作用及调脂疗效,以及对临床心血管事件影响。方法采用彩色多普勒超声检出颈动脉粥样硬化斑块形成者95例,随机分为对照组及治疗组;治疗组分别口服辛伐他汀20、40 mg共24周,观察治疗前后颈动脉内膜中层厚度(IMT),胆固醇(TC)、甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的变化以及冠心病事件的发生情况。结果辛伐他汀20mg及40 mg组均能显著消退颈动脉粥样硬化斑块,20mg组:IMT治疗后(1.21mm±0.17mm)比治疗前(1.49mm±0.26mm)减少(P<0.05)。40mg组:IMT治疗后(1.19mm±0.24mm)比治疗前(1.45mm±0.22mm)减少(P<0.05)。结论辛伐他汀对血脂正常老年冠心病患者仍有调节血脂作用,同时也可进一步减轻颈动脉粥样斑块厚度并能明显减少临床心血管事件的发生。     

中西医结合治疗对高脂血症患者血脂水平及颈动脉内膜中层厚度的影响

目的 :探讨健脾降浊汤联合辛伐他汀对高脂血症患者血脂水平、颈动脉内膜中层厚度(IMT)的影响。方法 :104例高脂血症患者按照随机数字表法分为观察组53例和对照组51例,对照组给予辛伐他汀片20 mg睡前口服,观察组在对照组的基础上加用健脾降浊汤,每次200 m L,日2次;分别于治疗前、治疗后8周检测患者血脂水平、颈动脉IMT。结果:两组患者三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平均下降,与治疗前比较,差异有统计学意义(P0.05);观察组治疗后TG、TC、LDL-C水平明显低于对照组,差异有统计学意义(P0.05),但HDL-C水平较对照组升高不明显,差异无统计学意义(P0.05)。两组患者治疗后颈动脉IMT均降低,与治疗前比较,差异有统计学意义(P0.05);观察组治疗后颈动脉IMT明显低于对照组,差异有统计学意义(P0.05)。对照组1例患者出现不良反应,观察组未出现不良反应。结论:健脾降浊汤联合辛伐他汀片能显著降低血脂水平,改善颈动脉IMT,具有较强的调脂及抗动脉硬化作用。