基于近红外光谱法的阿托伐他汀钙片质量一致性评价及含量快速测定

目的：建立近红外光谱法对阿托伐他汀钙片进行质量一致性评价及有效含量的快速测定。方法：采用便携式近红外光谱仪,采集23批阿托伐他汀钙片样品的漫反射近红外光谱数据,使用主成分分析（principal component analysis,PCA）建立不同批次阿托伐他汀钙片样品的质量一致性评价模型。使用不同光谱预处理方法对原始光谱进行光谱预处理,采用组合区间偏最小二乘（synergy interval partial least squares,SiPLS）算法对建模波数区间进行优化,并以高效液相色谱（high performance liquid chromatography,HPLC）法为参考方法,建立阿托伐他汀钙片的近红外定量分析模型。结果：使用不同批次阿托伐他汀钙片的光谱信息建立的PCA模型分类效果良好。对不同的光谱预处理方法进行比较,得到光程散射校正（multiplicative scattering correction,MSC）为最佳光谱预处理方法。当全光谱划分为30个区间时,选择3个子区间进行组合可得到最佳建模波数范围。校正模型的交叉验证均方根误差（root mean square error of cross-validation,RMSECV）为1.230 2,交叉验证相关系数（correlation coefficient of cross-validation,R_CV）为0.914 6,预测模型的预测均方根误差（root mean square error of prediction,RMSEP）为1.676 4,预测相关系数（correlation coefficient of the prediction,R_P）为0.964 2。结论：该研究建立的定性和定量方法准确、可靠,可以快速进行阿托伐他汀钙片的质量一致性评价及含量测定。     

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-β were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-β in dialysate may be one of the possible underlying mechanisms.     

An open-label, uncontrolled, prospective study of the effects of atorvastatin 10 mg on low-density lipoprotein cholesterol levels in chinese adults with coronary artery disease and hypercholesterolemia

Background: A high level of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary artery disease (CAD). Evidence shows that lowering LDL-C improves the outcomes of patients with CAD. Atorvastatin is an established drug for the treatment of hypercholesterolemia.Objective: The purpose of this open-label, uncontrolled, prospective study was to assess the effectiveness of treatment with atorvastatin 10 mg/d for 18 weeks in achieving the target level of LDL-C (<2.6 mmol/L [<100 mg/dL]) established by the National Cholesterol Education Program (NCEP) (United States) for patients with established CAD and hypercholesterolemia.Methods: Chinese patients with CAD, hypercholesterolemia (defined as a baseline LDL-C level between 3.4 and 5.2 mmol/L [131-201 mg/dL]), and body mass index <30 kg/m² were eligible. Atorvastatin 10 mg/d was given to each patient for 18 weeks. Lipid profiles were checked at 6, 12, and 18 weeks. To assess the extent of the achievement of NCEP LDL-C target levels, patients were categorized into 3 groups retrospectively according to baseline LDL-C level: group 1, 3.4 to 4.0 mmol/L (131-154 mg/dL); group 2, 4.01 to 4.6 mmol/L (155-178 mg/dL); and group 3, 4.61 to 5.2 mmol/L (179-201 mg/dL).Results: A total of 63 patients (50 men, 13 women; mean age, 64.3 years) were enrolled. Significant decreases in total cholesterol (31.3% at week 18), LDL-C (42.9% at week 18), and triglycerides (21.8% at week 18) from baseline levels were found at 6, 12, and 18 weeks of treatment (P < 0.001 for all). The changes in high-density lipoprotein cholesterol levels were nonsignificant. In group 1, 83.3% of patients met the target level of LDL-C; group 2, 87.5%; group 3, 37.5%; groups 1 and 2 combined, 85.2%. Atorvastatin 10 mg/d was well tolerated. Clinical adverse events were mild and transient; no severe adverse events were reported. One patient (1.6%) developed an elevated alanine aminotransferase level and withdrew. Sixty-two of 63 patients (98.4%) completed the study.Conclusions: In this group of Chinese patients with CAD and hypercholesterolemia treated with atorvastatin 10 mg/d for 18 weeks, 85.2% of patients with a baseline LDL-C level of 3.4 to 4.6 mmol/L achieved the NCEP target LDL-C level of <2.6 mmol/L, suggesting that atorvastatin 10 mg/d is efficacious in preventing secondary CAD.     

The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity

Aims

Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).

Methods

In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day⁻¹ (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.

Results

Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.

Conclusions

The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.     

缬沙坦联合阿托伐他汀治疗慢性肾炎的临床疗效观察

目的探讨缬沙坦联合阿托伐他汀治疗慢性肾炎的临床疗效。方法将168例慢性肾炎患者随机分入A组与B组,两组患者均接受慢性肾炎常规治疗。A组患者同时接受口服缬沙坦,B组患者接受缬沙坦及阿托伐他汀口服,疗程12月。比较两组治疗前后肾功能、24 h尿蛋白定量、超敏C反应蛋白、肾小球滤过率(GFR)、血脂、血压、肝功能及肌酶等差别。结果治疗12个月后,B组hs-CRP、24h尿蛋白显著优于A组(P<0.05),B组胆固醇及低密度脂蛋白显著降低(P<0.05),两组收缩压、舒张压、肝功能、肌酶水平比较差异无统计学意义(P>0.05)。结论缬沙坦联合阿托伐他汀治疗慢性肾炎可显著降低CRP水平并减少尿蛋白,有利于延缓病情。     

氨氯地平联合阿托伐他汀对高血压合并高血脂症患者的疗效

目的:探究氨氯地平联合阿托伐他汀在治疗高血压合并高血脂症中的临床疗效.方法:门诊治疗的高血压合并高血脂症患者200例,随机均分为观察组和对照组,观察组患者采用氨氯地平联合阿托伐他汀治疗,对照组患者采用氨氯地平进行治疗;观察两组患者治疗前后血压变化,比较治疗效果;同时比较两组患者治疗前后的低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)及胆固醇(TC),丙氨酸氨基转移酶(ALT)、血肌酐、血钾(K+)及血尿酸水平.结果:治疗后,观察组总有效率优于对照组,不良反应明显低于对照组(P＜0.05),收缩压和舒张压较治疗前明显下降,观察组改善更明显(P＜0.05);观察组患者LDL-C、TG及TC水平较治疗前下降,而HDL-C升高,这些血脂成分改变优于对照组(P＜0.05);观察组治疗后,血肌酐和血尿酸水平下降明显(P＜0.05),与无变化的对照组间比较,差异有统计学意义(P＜0.05).结论:氨氯地平联合阿托伐他汀对高血压合并高血脂症患者的治疗效果优于单独使用氨氯地平.