卡维地洛对充血性心力衰竭患者心肌肌钙蛋白I及心功能的影响

目的：观察卡维地洛对充血性心力衰竭（CHF）患者心肌肌钙蛋白I（cTnI）及心功能的影响。方法：将42例CHF患者随机分为对照组和实验组，两组疗程均为2周。观察治疗前后cTnI以及左室射血分数、左室短轴缩短率、每搏出量、心输出量及心脏指数等指标变化情况。结果：经治疗2周后，实验组总有效率显著高于对照组，两组比较差异有统计学意义（P〈0．05）；治疗后两组患者cTnI较治疗前显著降低，实验组优于对照组（P〈0．05或P〈0．01）。结论：CHF患者存在cTnI异常，卡维地洛可纠正CHF患者异常的cTnI水平，改善心功能。     

β受体阻滞剂治疗慢性心力衰竭的临床观察

目的观察慢性充血性心力衰竭在常规抗心衰治疗基础上，加用非选择性β受体阻滞剂（卡维地洛）115床疗效。方法选择CHF病人80例，随机分为两组，对照组39例，常规抗心衰治疗（强心、利尿、扩血管＋血管紧张素转换酶抑制剂ACEI或血管紧张素Ⅱ受体拮抗剂；观察组41例，在常规抗心衰治疗基础上，加用卡维地洛，观察4周，随访18个月。前后对比心功能、血压、心率、左室收缩末内径、左室射血分数、脑利钠肽前体、高敏C反应蛋白的变化。结果治疗组心功能明显改善，再住院率下降，治疗组与对照组疗效有显著性差异（P〈0．05）。结论CHF患者，在抗心衰基础上，常规加用β受体阻滞剂是一种安全、有效的方法。     

贝那普利与卡维地洛联合应用治疗充血性心力衰竭

目的:观察血管紧张素转换酶抑制剂(ACEI)贝那普利和非选择性β-受体阻滞剂卡维地洛联合应用治疗慢性充血性心力衰竭(CHF)患者的临床疗效。方法:利用贝那普利和卡维地洛联合治疗CHF患者36例,并与单用贝那普利治疗CHF患者32例进行疗效比较。结果:治疗组与对照组有效率分别为94.4%和68.8%(P<0.05),两组有显著性差异。结论:贝那普利和非选择性β-受体阻滞剂卡维地洛联合应用是治疗慢性充血性心力衰竭安全有效的方法。     

贝那普利与卡维地洛联合治疗慢性心力衰竭的临床观察

目的：观察贝那普利和卡维地洛联合应用治疗慢性心力衰竭的临床疗效。方法：96例慢性心力衰竭患者随机分为贝那普利和卡维地洛联合治疗组（以下简称治疗组，48例）及贝那普利对照组（48例）。贝那普利对照组用药除无卡维地洛外余同联合治疗组。6个月为一疗程。观察用药前后收缩压（SBP）、舒张压（DBP）、心率（HR）、左室收缩末内径（LVESd）、左室舒张末内径（LVEDd）及左室射血分数（LVEF）的变化。结果：治疗组与对照组的总有效率分别为91．7％和72．9％（P〈0．05），治疗组与对照组治疗6个月后SBP、DBP、HR、LVESd、LVEDd均显著下降，LVEF显著增加；且治疗组上述指标改善更明显。结论：贝那普利联合卡维地洛治疗慢性心力衰竭安全有效，可明显提高慢性心力衰竭的疗效。     

卡维地洛对心肌梗死后窦性心率震荡的影响

目的 探讨卡维地洛对心肌梗死后窦性心率震荡的影响及窦性心率震荡与交感神经的关系.方法 入选急性心肌梗死患者66例,随机分为观察组与对照组,观察组予卡维地洛治疗12个月,对照组则常规予以美托洛尔治疗12个月,所有病例于β-受体阻滞剂治疗前、治疗后6个月、12个月行24 h Holter检查及血浆去甲肾上腺素(NE)和肾上腺素(E)量的检测,随访新的心脏事件发生情况.用ECGLAB TOP版HOLTER软件取得窦性心率震荡参数:震荡起始(TO)及震荡斜率(TS)值,分析比较两组各阶段数值、新的心脏事件发生率及TO、TS值与血浆NE和E间相关性.结果 β-受体阻滞剂治疗前,两组TO、TS、血浆NE和E量差异均无统计学意义.在治疗6个月及12个月后,对应阶段观察组NE、E量、TO值显著低于对照组,TS显著高于对照组(P＜0.05).治疗后观察组NE、E及TO值逐步显著下降,TS逐步显著上升,三个阶段的差异有统计学意义(P＜0.05);对照组NE和E有所下降,TS有所上升,但三个阶段的差异无统计学意义(P＞0.05).随访12个月中,观察组新的心脏事件发生率亦显著低于对照组(P＜0.05).TO、TS与NE、E指标之间的存在显著相关性(P＜0.05).结论 卡维地洛可阻滞心肌梗死后交感神经分泌,可能更有效地预防心肌梗死后新的心脏事件发生;交感神经分泌的变化在窦性心率震荡过程中起重要作用,窦性心率震荡的变化可能对新的心脏事件发生有预测价值.     

厄贝沙坦联合卡维地洛治疗慢性心衰的疗效观察

目的研究厄贝沙坦与卡维地洛联合应用在慢性心衰患者中的疗效。方法90例慢性心衰患者,随机分成厄贝沙坦＋卡维地洛组（实验组,45例）、卡托普利＋倍他乐克组（对照组,45例）。治疗前、治疗3个月后通过彩色多普勒超声心动图来评价其心功能情况,检测指标包括左室射血分数（LVEF）、左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）,血清BNP及6min步行实验,并进行比较。结果二组患者治疗后各项指标均有不同程度改善,实验组各指标包括LVEDD、LVESD、LVEF、BNP改善更为明显[（52．8±3．4）VS（57．4±3．7）,P=0．034;（41．3±2．7）vs（46．6±3．9）,P=0．021;（42．3±3．4）VS（30．6±3．8）,P=0．014;（463．8±56．34）VS（508．3±52．74）,P=0．017,特别是患者6min步行实验结果（491．5±6．2VS415．4±5．5,P=0．008]。结论厄贝沙坦联合卡维地洛治疗更能改善慢性心衰患者心功能。     

Are generic formulations of carvedilol of inferior pharmaceutical quality compared with the branded formulation?

ABSTRACT

Introduction: Carvedilol is a comprehensive β₁?, β2? and α₁-adrenoreceptor blocker marketed as Dilatrend by F. Hoffmann-La Roche Ltd. (Roche) and as Coreg by GlaxoSmithKline for the treatment of hypertension, stable angina pectoris, post myocardial infarction with left ventricular dysfunction and all degrees of symptomatic chronic heart failure.

Objectives: In this report, the pharmaceutical qualities of Dilatrend 6.25?mg, 12.5?mg and 25?mg tablets and 35 randomly selected carvedilol generic products from 20 manufacturers in 19 countries have been assessed according to the European Pharmacopoeia and the Roche specifications.

Methods: The generic products were subjected to four key tests: carvedilol content, tablet hardness, tablet dissolution and purity.

Results: All three Dilatrend strengths conformed to specifications. At least 17/35 (48.6%) generic products failed the specifications due to: incorrect mean carvedilol content (outside 95–105%) – three products; excess impurities (> 0.3%) – one product; incorrect tablet hardness (outside 30–70?N) – 11 products; inadequate dissolution (< 75% in 30?min) – nine products. Seven products (20%) failed two tests, generally hardness and dissolution.

Conclusion: The dose-for-dose substitution of the original formulation of carvedilol (Dilatrend) with a pharmaceutically different, and possibly inferior, generic copy may conceivably result in a change in the efficacy of the treatment, because of an unanticipated change in pharmacokinetics or bioequivalence, and/or in a change in tolerability due to impurities.     

Novel lectin-modified poly(ethylene-co-vinyl acetate) mucoadhesive nanoparticles of carvedilol: preparation and in vitro optimization using a two-level factorial design

Abstract

Carvedilol used in cardiovascular diseases has systemic bioavailability of 25–35%. The objective of this study was production of lectin-modified poly(ethylene-co-vinyl acetate) (PEVA) as mucoadhesive nanoparticles to enhance low oral bioavailability of carvedilol. Nanoparticles were prepared by the emulsification-solvent evaporation method using a two-level factorial design. The studied variables included the vinyl acetate content of the polymer, drug and polymer content. Surface modification of PEVA nanoparticles with lectin was carried out by the adsorption method and coupling efficiency was determined using the Bradford assay. Mucoadhesion of nanoparticles was studied on mucin. The particle size, polydispersity index, zeta potential, drug loading and drug release from nanoparticles were studied. The morphology of nanoparticles and crystalline status of the entrapped drug were studied by SEM, DSC and XRD tests, respectively. Results showed the most effective factor on particle size and zeta potential was the interaction of polymer and drug content while, drug loading efficiency and mucoadhesion were more affected by the interaction of polymer type and drug content. Drug concentration was the most effective variable on the drug release rate. The drug was in amorphous state in nanoparticles. The optimum nanoparticles obtained by 45?mg of copolymer contained 12% vinyl acetate/4.3?ml of organic phase and drug concentration of 37.5?wt% of polymer.     

A novel solubility-modulated granules through porosity osmotic pump for controlled carvedilol delivery

A method for the preparation of porosity osmotic pump granules was obtained by modulating carvedilol solubility with tartaric acid. Controlled porosity of the membrane was accomplished by the use of pore-forming agent in the coating. In this study, carvedilol was chosen as a model drug with an aim to develop a zero-order release system; tartaric acid was used as the solubility promoter; NaCl was used as the osmotic agent; cellulose acetate (CA) was used as the materials of semipermeable membrane; and PEG-400 was used as the pore-forming agent in the semipermeable membrane. The influence of different factors or levels on the in vitro release was studied. In order to simulate the gastrointestinal tract environments, two kinds of pH media (pH 1.5 and 6.8) on drug release were studied in this research, respectively. This porosity osmotic pump was optimized by single factor design experiments, and it was found to deliver carvedilol at a zero-order rate within 12?h and controlled release for 24?h. We drew a conclusion that the solubility-modulated porosity osmotic pump system is simple to prepare and might be used for the preparation of osmotic pump system of other poorly water-soluble drugs with alkaline or acid groups.     

急性病毒性心肌炎小鼠肿瘤坏死因子-α、单核细胞趋化蛋白-1的表达及卡维地洛的干预作用

目的 探讨TNF-α、单核细胞趋化蛋白-1(MCP-1)在急性病毒性心肌炎(VMC)发病中的作用及β受体阻滞剂卡维地洛对其影响.方法 将80只4周龄雄性Balb/c小鼠随机分为3组:心肌炎组(n=30)、卡维地洛组(n=30)和对照组(n=20),心肌炎组及卡维地洛组经腹腔接种柯萨奇病毒B3(CVB3)诱发急性VMC,对照组接种不含病毒的Eagle's液;卡维地洛组于接种病毒次日开始灌服卡维地洛5 mg/kg,心肌炎组和对照组灌服9 g/L盐水,每天2次.于接种后的第7、14天随机从各组抽取8只小鼠取血后处死,HE染色检测小鼠心肌病理积分,ELISA法检测血清TNF-α水平,RT-PCR检测心肌组织MCP-1 mRNA的表达.结果 心肌炎组心肌组织病理积分较对照组明显增高(P＜0.01),卡维地洛组较心肌炎组病理积分降低(P＜0.05);心肌炎组小鼠血清TNF-α水平较对照组升高(P＜0.01),且与心肌病理积分呈正相关(r=0.42,P＜0.05),卡维地洛组TNF-α水平较心肌炎组显著下降(P＜0.05);与对照组比较,心肌炎组小鼠心肌MCP-1 mRNA表达明显增加(P＜0.01),卡维地洛组小鼠心肌MCP-1 mRNA表达较心肌炎组明显下降(P＜0.05).结论 TNF-α和MCP-1参与VMC的发病过程,卡维地洛可能通过下调TNF-α、MCP-1的过表达减轻CVB3感染小鼠的心肌损害,起心肌保护作用.