瑞舒伐他汀对高血压合并高脂血症患者血压的影响

目的 观察瑞舒伐他汀对高血压合并高脂血症患者血压的影响.方法 选择首次诊断为高血压合并高脂血症的患者120例.随机分为治疗组(58例)和对照组(62例),对照组给予常规降压药物治疗,治疗组在常规治疗基础上加用瑞舒伐他汀10mg/d口服.测定治疗前后动态血压水平,血中低密度脂蛋白胆固醇(LDL-C)、高敏C反应蛋白(hs-CRP)、血浆内皮素水平.结果 治疗1月后,两组血压均较治疗前明显降低(P<0.05),治疗组血压下降更明显(P<0.05);治疗组血中LDL-C和hs-CRP、内皮素水平较治疗前明显降低(P<0.05),与对照组比较差异也有显著性(P<0.05).结论 应用瑞舒伐他汀可降低高血压患者血中LDL-C和hs-CRP、内皮素水平,进一步降低血压.     

联合应用瑞舒伐他汀和红霉素对不稳定斑块中基质金属蛋白酶-2表达的影响

目的探讨瑞舒伐他汀和红霉素对兔动脉粥样硬化不稳定斑块中基质金属蛋白酶-2（matrix met-alloproteinase,MMP-2）表达的影响,以及联合应用红霉素后抑制MMP-2表达的作用是否增强。方法健康雄性新西兰大白兔40只,随机分为空白对照组（Control组,n=10）、不稳定斑块组（VAS组,n=10）,瑞舒伐他汀组（RSV组,n=10,1mg/kg/d）及瑞舒伐他汀＋红霉素组（RSV＋EM）组（n=10,1mg/kg/d＋1mg/kg/d）,饲养8周后,免疫组化方法观察各组腹主动脉斑块中MMP-2的表达。结果 RSV组及RSV＋EM组较VAS组不稳定斑块中MMP-2表达减少;RSV＋EM组较RSV组MMP-2表达减少,具有统计学意义（P﹤0.05）。结论瑞舒伐他汀通过抑制MMP-2的表达来稳定动脉粥样斑块,联合应用红霉素具有协同作用。     

Clinical efficacy of rosuvastatin in lipid management in Chinese patients in Hong Kong

Background Rosuvastatin has been claimed to be more potent than other statins in its ability to lower the low-density lipoprotein （LDL） cholesterol levels. This study aimed to investigate the clinical efficacy of rosuvastatin in LDL cholesterol lowering therapy for new or switched hyperlipidaemic Chinese patients. Methods This study was a retrospective one in patients who took rosuvastatin in the outpatient clinics of Prince of Wales Hospital during the period of July 1,2004 to June 30, 2005. The prescribing pattern, the utilization pattern and the side effect profile were recorded. Attainment of lipid goals for each patient was assessed according to the National Cholesterol Education Program Adult Treatment Panel （NCEP ATP） III guidelines. Results A total of 261 Chinese patients （mean age （64.8±12） years; 55.6% male） were recruited into the study. The mean LDL-cholesterol level was （3.50±1.29） mmol/L prior to Rosuvastatin and （2.30±1.73） mmol/L after Rosuvastatin treatment （P 〈0.0001）. Rosuvastatin raised the LDL-cholesterol goal achievement rate from 28.0% to 74.3% in all patients combined （P 〈0.0001） and from 11.0% to 79.0% for statin naive patients （P 〈0.0001）. Approximately 4% of patients developed side effects including myalgia, elevated liver enzymes, and dizziness. Conclusion Rosuvastatin was effective in improving LDL-cholesterol goal attainment and lowering LDL-cholesterol and triglyceride （TG） levels in either newly started or switched patients.     

No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin

AIMS

This study aimed to investigate possible effects of ABCB1 genotype on fluvastatin, pravastatin, lovastatin, and rosuvastatin pharmacokinetics.

METHODS

In a fixed-order crossover study, 10 healthy volunteers with the ABCB1 c.1236C/C-c.2677G/G-c.3435C/C (CGC/CGC) genotype and 10 with the c.1236T/T-c.2677T/T-c.3435T/T (TTT/TTT) genotype ingested a single 20-mg dose of fluvastatin, pravastatin, lovastatin, and rosuvastatin. Plasma fluvastatin, pravastatin, and lovastatin concentrations were measured up to 12 h and plasma and urine rosuvastatin concentrations up to 48 and 24 h, respectively.

RESULTS

The ABCB1 genotype had no significant effect on the pharmacokinetics of any of the investigated statins. The geometric mean ratio (95% confidence interval) of the area under the plasma concentration–time curve from 0 h to infinity (AUC_0–∞) in participants with the TTT/TTT genotype to that in those with the CGC/CGC genotype was 0.96 (0.77, 1.20; P= 0.737) for fluvastatin, 0.92 (0.53, 1.62; P= 0.772) for pravastatin, 0.83 (0.36, 1.90; P= 0.644) for lovastatin, 1.25 (0.72, 2.17; P= 0.400) for lovastatin acid, and 1.10 (0.73, 1.65; P= 0.626) for rosuvastatin. The AUC_0–∞ of lovastatin acid correlated significantly with that of rosuvastatin (r= 0.570, P= 0.009), but none of the other AUC_0–∞ pairs showed a significant correlation.

CONCLUSIONS

These data suggest that the ABCB1 c.1236C-c.2677G-c.3435C and c.1236T-c.2677T-c.3435T haplotypes play no significant role in the interindividual variability in the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin.     

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。     

Combination Therapy of Rosuvastatin and Ezetimibe in Patients with High Cardiovascular Risk

Purpose

The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk.

The role of OATP1B1 and BCRP in pharmacokinetics and DDI of novel statins

The aim of this review is to provide useful information not only for studying the effect of OATP1B1 and/or BCRP gene mutation on pharmacokinetics of novle statins of pitavastatin and rosuvastatin but also for studying drug-drug interactions (DDI) between the novle statins and other substrates of OATP1B1 and/or BCRP. Intra- and inter-ethnic differences in pharmacokinetic profiles of clinically relevant drugs are important issues reported in many papers not only for scenes of appropriate drug used in clinical settings but also for those of the drug development. Pharmacogenomics is extremely useful for understanding these racial differences. Recent pharmacogenetics study have disclosed important roles of drug transporters in the pharmacokinetic (PK) profiles of some clinically relevant drugs. In this presentation, we introduce single nucleotide polymorphisms (SNPs) of OATP1B1 and BCRP and review the contribution of genetic polymorphisms of the transporters to the pharmacokinetics of dual substrates as pitavastatin and rosuvastatin from recent study. At the same time, the DDIs between pitavastatin or rosuvastatin and other drug have been extensively concerned because of inhibiting OATP1B1-mediated hepatic uptake or BCRP-mediated hepatic efflux of pitavastatin and rosuvastatin. This review summarized the current studies about the role of OATP1B1 and BCRP in DDIs between pitavastatin or rosuvastatin and other clinically relevant drugs. The role of OATP1B1 and BCRP gene mutation can affect the PK profiles of pitavastatin and rosuvastatin. The DDIs between the novle statins and other substrates of OATP1B1 or BCRP may occur and cause change in the pharmacokinetic of the novle statins.     

瑞舒伐他汀对急性冠状动脉综合征合并心律失常患者血脂和炎症因子的调节作用研究

目的：探讨瑞舒伐他汀对急性冠状动脉综合征（ACS ）合并心律失常患者血脂和炎症因子的调节作用。方法于2010年2月至2012年12月,将102例ACS合并心律失常患者分为A组和B组,每组患者51例。A组给予瑞舒伐他汀组治疗,B组给予阿托伐他汀治疗。比较两组患者治疗前后低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、白细胞介素-18和C反应蛋白水平。结果两组患者治疗后血脂及炎症指标水平与治疗前比较差异均有统计学意义,且治疗后A组血脂及炎症指标改善程度均较B组更为明显（P＜0．05）。结论瑞舒伐他汀对ACS合并心律失常患者体内脂代谢水平和炎症状态均有一定的调节作用,可用于ACS合并心律失常患者的临床治疗。     

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。