他汀类药物代谢相关基因多态性与疗效和安全性的关联

他汀类药物是目前最有效的降低LDL-C水平从而降低心血管疾病风险的药物。但是,不同个体对不同他汀类药物的反应不同;导致差异的关键因素是他汀类药物在肝脏代谢和转运的遗传特性不同。特别是参与他汀类药物肝脏代谢的关键性转运蛋白如阴离子转运多肽(OATP1B1)(由SLCO1B1基因编码)以及乳腺癌抑制蛋白(BCRP)的基因多态性可影响他汀类药物的血浆及肝脏浓度,从而影响他汀类药物的疗效和安全性。他汀类药物在肌病风险或在降LDL-C的能力方面如发生变化,均会改变这类药物临床应用时的效益风险比,而且还会影响以开发新治疗为目的临床试验中他汀类药物的应用。     

他汀类药物临床应用及不良反应对策

他汀类药物属于3-羟基-甲基戊二酸辅酶A还原酶抑制剂．已在临床上广泛应用,大多用于降血脂和减低动脉粥样硬化的发生率。他汀类药物临床耐受性较好,在临床应用的安全性相对较理想,但也有相应不良反应,主要是对肝脏酶类和肌肉的毒性。作者结合本院情况,将他汀类药物的临床应用和不良反应情况分析如下。     

他汀类药物的应用现状及安全性问题

本文简述了他汀类药物应用的现状及存在的安全性问题，提醒应当关注和重视他汀类使用的安全性．强调建立完善他汀类药物临床监测并总结意见，反映了当前针对问题的一些经验，供临床应用参考。     

他汀类药物防治缺血性卒中研究现状与展望

他汀类药物是目前降低低密度脂蛋白胆固醇最有效的药物,其在缺血性卒中防治中有广泛应用。本文就他汀类药物防治缺血性卒中临床证据及他汀类药物的安全性进行了综述。     

他汀类药物安全性

他汀类药物通过其有效地降低总胆固醇和LDL胆固醇及药物对动脉粥样硬化的直接作用,在正常和高血脂个体的一、二级预防中,显著降低冠脉突发事件和冠脉性死亡,降低总死亡率.随着这类药物的广泛应用,其安全性越来越受到人们的重视.他汀类药物的毒副作用可能对机体的肝脏功能及骨骼肌、视觉系统、中枢神经系统造成损伤,但通常状态下,这些毒副作用的发生率较低,多为可逆性损害,不会对机体造成很大的损伤,药物的临床效益远远大于其毒副作用的风险.不同类型他汀类药物的毒副作用也不相同.近来,他汀类药物的肌肉毒性及由此引起的肾功能衰竭已经受到人们的重视,有关机制有待于进一步研究.临床上合理、准确地选择药物,严格控制药物剂量、避免药物间相互作用,将有利于控制或减少药物毒副作用的发生.     

他汀类药物安全性再认识

他汀类药物在动脉粥样硬化性心血管疾病(ASCVD)一线用药,随着他汀类药物的广泛长期应用,研究者们开始质疑其安全性,他汀类药物除了对肝脏和肌肉潜在的不良反应外,而近年来对于其是否引起肾脏损害、认知功能缺陷、新发肿瘤和糖尿病的风险成为研究者关注的热点.经过大量的研究和荟萃分析发现,他汀类药物引起肾脏功能损害、认知功能改变和引发肿瘤的证据还不充分,但有增加新发2型糖尿病的风险,而与他汀类药物保护心血管的作用相比,新发糖尿病风险表现的微乎其微.     

他汀类与心血管药物配伍的安全性分析

目的分析与研究他汀类与心血管药物配伍的安全性。方法分析他汀类和肾素及血管紧张素的转化酶抑制剂、钙拮抗剂、洋地黄类药物、抗心律失常类药物及其他降血脂类药物的配伍情况,并对其安全性进行总结。结果他汀类与肾素及血管紧张素的转化酶抑制剂、钙拮抗剂、洋地黄类药物及其他降血脂类药物配伍的安全性较好,但和抗心律失常类药物配伍需慎重。结论要重视他汀类和心血管类药物的配伍使用,如有需要可在剂量上加以调整,还需注意使用药物疗效的相互影响。     

他汀类药物与其他药物联用的安全性评价

目的对门诊处方中他汀类药物与其他药物联用的安全性进行评价,以利临床合理用药。方法抽查门诊使用他汀类药物的处方,以药品说明书中的规定为标准,结合近年来公开发表的相关文献,分析他汀类药物与其他药物联用的安全性。结果他汀类药物与其他药物联用基本合理,没有发现联用CYP3A4抑制剂,但有5种CYP3A4底物和地高辛与他汀类药物联用,存在安全隐患。结论他汀类药物与其他药物联用时应注意观察,避免与CYP3A4抑制剂或其底物联用。     

瑞舒伐他汀药代动力学及与其他药物的相互作用研究进展

瑞舒伐他汀是新一代他汀类药物,相对之前的他汀类药物,肝选择性更好;肝代谢少、消除半衰期长,具有更强的降脂作用,临床应用前景广泛;其耐受性良好,不良反应发生率与同类其他药物相似。本文对瑞舒伐他汀的药代动力学及与其他药物相互作用作一综述。以期为指导瑞舒伐他汀的临床用药打下坚实的理论基础,确保临床用药的安全性和有效性,真正实现临床上的个体化给药。     

氟伐他汀治疗原发性高胆固醇血症的疗效观察

他汀类药物不仅具有降脂作用。而且具有改善血管内皮功能、抗炎与稳定斑块作用，但是不同的他汀类药物具有不同的药理学特性和临床特性，我们的研究旨在进一步对氟伐他汀作出临床疗效和安全性评价。     

Implementation of a therapeutic-interchange clinic for HMG-CoA reductase inhibitors.

A therapeutic-interchange clinic for statins is described. In 1999, the Department of Defense mandated the use of cerivastatin and simvastatin as the formulary statins in all military health care facilities by April 2000. Cerivastatin was the preferred agent; the goal was to use this agent in 60-65% of all patients. Walter Reed Army Medical Center developed a voluntary therapeutic-interchange clinic for patients receiving statins. Goals included facilitating the rapid switching of patients to the formulary statins, maximizing the use of the preferred agent, maintaining or improving lipid control, monitoring safety, determining costs, educating patients about their treatment, and documenting satisfaction with the clinic. Written educational materials were prepared, an algorithm for statin conversion was created, and laboratory tests were performed, among other measures. Between January and April 2000, 1356 patients were seen by the therapeutic-interchange clinic; of these, 942 agreed to have the efficacy and safety of their therapy monitored by the clinic. Before the formulary change, the most commonly prescribed statins were atorvastatin (44% of patients) and pravastatin (42%). Under the conversion policy, 96% of patients received cerivastatin and 4% simvastatin. The percentage of patients achieving their targeted low-density-lipoprotein cholesterol concentration increased from 65% to 75%. The policy saved an average of $115 per patient in the first year. Most patients were satisfied with the clinic, but only 36% of providers were satisfied. Cerivastatin was withdrawn from the market in August 2001; simvastatin became the only formulary statin. A therapeutic-interchange clinic at a military medical center provided an efficient means of switching a large number of patients to alternative statin therapy, monitoring the outcomes, and individualizing patient care.     

The safety of rosuvastatin: effects on renal and hepatic function

Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been shown to reduce elevated serum cholesterol resulting in a reduced risk of coronary artery disease and its complications. Rosuvastatin is the latest of the class of HMG-CoA reductase inhibitors and has the most potent reduction of low-density lipoprotein and elevation of high-density lipoprotein in the class. Questions have been raised about its safety. In a careful examination of the data, rosuvastatin has the same rate of elevations of hepatic enzymes as the other statins. Whether any of the statins actually cause significant liver injury is doubtful, and this raises questions about the usefulness of routine monitoring of liver enzymes in statin patients. Rosuvastatin has been noted to produce low levels of transient proteinuria. However, transient proteinuria is seen with other comparable statins. Long-term administration of rosuvastatin and other statins have been shown not to be associated with any decline in renal function, but instead have been shown to produce modest but clear improvement in glomerular filtration rate. Therefore, it is clear that rosuvastatin, and other statins, are very safe and useful agents and do not appear to present significant risks to hepatic or renal safety.     

他汀类药物的不良反应

他汀类药物是临床广泛应用的降脂药,在多种心血管疾病的治疗中发挥重要作用。随着使用范围和使用人数的增加,其不良反应报道逐渐增多,包括他汀类药物相关性肌病、肝损害、过敏反应、眼外肌麻痹、性功能障碍、多尿、消化系统反应、关节痛、下肢不宁综合征等。本文对他汀类药物的不良反应和防治措施进行简要综述,以促进其合理应用。     

Drug–drug interaction with statins

3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors (the so-called statins: atorvastatin, fluvastatin, pravastatin, lovastatin, rosuvastatin and simvastatin) are a well-established class of drugs in the treatment of hypercholesterolemia. Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Since statins are prescribed on a long-term basis, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. Moreover, a combination of therapy between statins and other classes of lipid-lowering agents (e.g., ezetimibe, fibrates, resins and nicotinic acid) is recommended for some patients by current guidelines. Therefore, the potential for drug–drug interactions emerges as a relevant factor in determining the safety profile of statins. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions.     

The pleiotropic effects of statins and omega-3 fatty acids against sepsis: a new perspective

The available therapeutic options for sepsis are restricted by their effectiveness and high cost. Emerging preliminary data suggest that statins and omega-3 fatty acids (OM3FA) may be associated with improved outcomes in terms of prevention and treatment of sepsis. We sought to review the current evidence on the effectiveness of their combined administration against sepsis, by carrying out a review of PubMed and Scopus databases for relevant studies, without imposing language or time restrictions. No clinical studies were identified regarding the effect of the combination treatment with statins and OM3FA on sepsis in terms of prevention or treatment. However, there is experimental evidence that both statins and OM3FA inhibit the inflammatory process at different levels, but also enhance inhibition at those levels that are common. There are also preliminary data supporting the beneficial effect of this combination on platelet function and other haemostatic mechanisms. Appropriately designed and powered clinical trials are warranted to investigate the effectiveness and safety of the combined administration of statins and OM3FA for the prevention and treatment of sepsis.     

他汀类药物致不良反应文献分析

目的:探讨临床一线降脂药他汀类药物致不良反应的一般规律及特点,为临床合理用药提供参考。方法:对2000年～2005年国内报道的使用他汀类药物致不良反应19例进行分类统计、分析。结果:不良反应临床表现以肌肉毒性反应常见,其次为肝脏毒性反应以及其它不良反应(神经系统反应、关节肿痛、过敏等)。结论:应严格掌握用药指征、规范用药剂量及联合用药,密切观察患者临床表现及生化指标监测结果,确保其用药安全,减少不良反应的发生。     

New strategies to address drug-drug interactions involving OATPs

Pharmacokinetic drug-drug interactions (DDIs) are a major concern in drug development. Drug transport, along with drug metabolism via cytochrome P450s (CYPs), is increasingly being considered as an integral part of the overall pharnmacokinetics profile of a drug. Inhibition of transporters can lead to altered pharmacokinetics, potentially interfering with drug safety and efficacy. There is an increasing number of DDIs observed with statins, which are widely used in combination therapies, and this can be partly attributed to inhibition of individual hepatic transporters. Studies of these inhibitory interactions in vitro has indicated the importance of both hepatic solute carriers of the organic anion transporting polypeptide (OATP) superfamily and CYP inhibition. Mathematical models have been developed to gain more quantitative insights into the interplay between transport and metabolism of drugs. This article reviews new developments in the area of in vitro tools and modeling approaches that are used to study DDIs related to OATP transporters, with a focus on the clinical relevance of the transport-mediated DDIs involving statins.     

他汀类药物代谢相关基因多态性与其不良反应发生的相关性

目的:为他汀类药物的临床精准用药,预防和减少不良反应(ADR)的发生提供参考。方法:收集近年来国内外有关他汀类药物基因多态性与其ADR的参考文献,对他汀类基因多态性与其ADR的相关性进行归纳和总结。结果:药物代谢酶和转运体的相关基因多态性是影响他汀类药物ADR发生的重要因素。结论:基因多态性研究可为预防他汀类药物的ADR提供参考依据,临床可在服用他汀类药物前对患者进行基因型检测,以降低ADR的发生率。     

Efficacy and safety of rosuvastatin in treatment of dyslipidemia.

PURPOSE: The chemistry, pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, dosage and administration, and place in therapy of rosuvastatin are reviewed. SUMMARY: Rosuvastatin, the latest statin to receive approved labeling by the Food and Drug Administration, has shown superior efficacy in lowering low-density-lipoprotein (LDL) cholesterol. At daily doses of 5-40 mg, rosuvastatin produces mean reductions in plasma LDL cholesterol of 45-63%, statistically greater than those achieved with equivalent doses of atorvastatin, simvastatin, and pravastatin. Rosuvastatin also improves triglyceride, non-high-density lipoprotein (HDL)-cholesterol, and HDL cholesterol levels to produce a more favorable lipid profile. Rosuvastatin's safety was studied in more than 10,000 patients, exceeding the number of patients evaluated before the launch of any other statin. Many of these patients took the drug for up to 96 weeks. With regard to muscle, renal, and hepatic toxicity and the withdrawal rate due to adverse events, rosuvastatin demonstrates a safety profile similar to that of the other marketed statins. Rosuvastatin undergoes only minor metabolism (10% of the administered dose) by the cytochrome P-450 2C9 isoenzyme. Significant drug interactions were reported with cyclosporine, gemfibrozil, warfarin, and antacids. Evidence suggests that rosuvastatin will be a valuable addition to the choices for treatment of patients with dyslipidemia. CONCLUSION: Rosuvastatin has greater efficacy in lowering LDL cholesterol and non-HDL-cholesterol concentrations than the other statins. It has been shown to enable more patients to reach their LDL cholesterol goals than other statins and to do so with an acceptable safety profile.     

2009年至2011年我院门诊药房调血脂药应用分析

目的评价武汉大学人民医院门诊药房调血脂药的应用情况及趋势,为临床合理用药提供参考。方法采用限定日剂量方法,对门诊药房2009年至2011年调血脂药的销售金额、用药频度（DDDs）及限定日费用（DDC）等指标进行统计、分析。结果调血脂药的销售金额和DDDs呈逐年上升趋势,其中他汀类、贝特类药销售金额增幅明显,年均增长率分别为28．85％,35．19％。结论医院调血脂药临床应用合理,他汀类、贝特类药占主导地位,高效、安全、依从性好的药物受到临床青睐。