卡维地洛对慢性心衰患者血浆脑钠肽水平及左心功能的影响

目的：观察卡维地洛对慢性心力衰竭（CHF）患者血浆脑钠肽（BNP）及左心室收缩功能的变化。方法：CHF患者87例,分卡维地洛治疗组（B组）44例和常规治疗组（A组）43例。随访6个月,评估两组治疗前、治疗后1个月、3个月及6个月患者心功能指标和血浆BNP浓度。结果：治疗后1个月两组血浆BNP水平较治疗前下降（P〈0．05）,3个月时下降更明显。3个月组间比较有显著性差异（P〈0．05）;两组患者治疗1个月后左心室舒张末内径（LVEDD）、左心室舒张末容积（LVEDV）、左心室收缩末容积（LVSDV）及左心室射血分数（LVEF）与治疗前比较均无统计学差异（P〉0．05）;6个月时的上述指标与治疗前比较均有显著性差异（P〈0．05）。两组患者血浆BNP水平与同期测定的左心室舒张末内径呈正相关（r=0．51,P〈0．01）,与LVEF呈负相关（r=-0．43,P〈0.01）。结论：卡维地洛能有效地改善CHF患者的心功能;CHF患者BNP水平的变化早于心脏超声指标的变化：血浆BNP水平可以作为治疗心力衰竭的一个可靠观察指标。     

Renal and cardiac function during α 1 -β-blockade in congestive heart failure

The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and &#103 -blockade. The need for control of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined &#102 1 - &#103 -blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function. Methods : Fourteen patients treated for moderate to severe CHF with diuretics and ACE inhibitors were investigated at baseline, after 4 months of maximum carvedilol treatment and after withdrawal of carvedilol. Results : Carvedilol lowered blood pressure and heart rate but increased left and right ventricular ejection fractions without changing cardiac output or pulmonary blood volume. At the same time, a minor fall was seen in glomerular filtration rate (GFR), but renal blood flow was unchanged and effective renal plasma flow slightly increased. Carvedilol also lowered the plasma levels of angiotensin II and aldosterone. All changes were reversed after withdrawal of carvedilol. Conclusions : Carvedilol augments ACE-inhibitor-induced vasodilation by lowering blood pressure, and angiotensin II beside reducing heart rate. The heart adapts to the haemodynamic alterations without changes in cardiac output and pulmonary blood volume. GFR is slightly lowered despite no changes in renal blood flow and a slight increase in effective renal plasma flow. The study emphasizes the need for control of renal function during treatment with carvedilol in patients with CHF.     

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.     

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.     

卡维地洛对舒张性心力衰竭患者血浆脑钠肽及心功能的影响

目的评价卡维地洛对舒张性心力衰竭(DHF)患者血浆脑钠肽及心功能的影响。方法 46例DHF患者,按入院顺序随机分为卡维地洛治疗组23例,对照组23例。两组均给予常规治疗,包括血管紧张素转换酶抑制剂、钙离子拮抗剂及利尿剂,治疗组在此治疗基础上加用卡维地洛6.25mg,2次/d,逐渐增至25mg,2次/d。治疗4周后随访8周,检测两组患者血浆脑钠肽浓度及左室射血分数(LVEF)。结果 8周后随访,与对照组比较,治疗组血浆脑钠肽浓度降低显著(P<0.01),LVEF增加明显(P<0.01),未见严重不良反应。结论卡维地洛能明显降低DHF患者血浆脑钠肽浓度,改善心功能,且安全有效。     

卡维地洛联合螺内酯治疗慢性心力衰竭的综合疗效观察

目的：探讨卡维地洛联合螺内酯治疗慢性心力衰竭的综合疗效。方法：选取2009年1月-2011年8月来我院附属医院进行治疗的120例慢性心力衰竭患者作为研究对象,将其随机分为对照组（常规治疗组）60例和观察组（卡维地洛联合螺内酯组）60例,将两组患者的治疗总有效率、不良反应发生率、治疗前及治疗后3、6个月的血清肌钙蛋白I（cTnI）、脑钠肽（BNP）、I型前胶原氨基端肽（PIP）及Ⅲ型前胶原氨基端肽（PIIIP）水平、左心房内径、左心室射血分数、室间隔厚度及左心室重量指数进行检测及比较。结果：观察组的治疗总有效率（98．33％）高于对照组（81．67％）,治疗后3、6个月cTnI[（0．35±0．09）、（0．20±0．14）mg／m11、BNP[（802．14±251．47）、（524．67±275．6）ng／ml]、PIP[（1102．45±286．54）、（742．50±263．54）pg／L]及PIIIP[（96．45±22．03）、（87．96±19．85）pg／L]水平低于对照组cTnI[（0．49±0．15）、（0．63±0．10）mg／m1]、BNP[（1102．45±286．54）、（742．50±263．54）ng／ml]、PIP[（132．05±16．03）、（121．06±15．58）ps／L]及PIIIP[（120．34±23．01）、（105．43±21．54）pg／L],左心房内径【（50．23±3．54）、（48．23±4．12）mm】及左心室重量指数[（112．64±4．86）、（104．75±4．97）gemS]±于对照组的[（55．64±4．13）、（52．09±3．64）mm],[（131．20±4．96）、（121．09±4．89）g／m^2],室间隔厚度[（9．89±0．65）、（11．02±0．73）mm]、左心室射血分数[（57．69±3．66）、（59．89±4．02）％]大于对照组的[（8．03±0．54）、（8．59±0．62）mml、[（53．68±3．67）（55．61±3．52）％1,差异均有统计学意义（P〈0．05）,但两组不良反应发生率比较（11．67％vs11．67％）,差异无统计学意义（P〉O．05）。结论：卡维地洛联合螺内酯治疗慢性心力衰竭的综合疗效较佳,在改善心功能及调节多项血清因子方面也有明显的效果。     

卡维地洛治疗慢性充血性心力衰竭的疗效观察

目的观察卡维地洛治疗慢性充血性心力衰竭（CHF）的疗效。方法 60例CHF患者随机分为治疗组与对照组,治疗组在常规治疗的基础上,从小剂量开始加用卡维地洛至目标剂量维持;对照组仅采用常规治疗。在治疗12个月后观察2组疗效。结果用药（卡维地洛）12个月后治疗组总有效率为93.3%,明显高于对照组的有效率（66.7%）,差异有统计学意义（χ^2=6.67,P〈0.01）。2组治疗后左室舒张末期内径（LVDd）、左室收缩末期内径（LVSd）、左室射血分数（LVEF）、心率（HR）的变化的差异均有统计学意义（P〈0.05）,结论在常规治疗基础上从小剂量开始加用卡维地洛治疗CHF,疗效均优于常规治疗,不良反应小,安全性高。     

螺内酯联合卡维地洛治疗难治性高血压的疗效观察

目的观察螺内酯联合卡维地洛治疗难治性高血压的临床效果。方法 62例难治性高血压患者,随机分成治疗组和对照组,各31例,治疗组给予卡维地洛12.5～25mg/d,螺内酯20～40mg/d,对照组给予卡维地洛25mg,1次/d。结果治疗组有效率为93.5%,对照组有效率为67.7%(P<0.05)。结论卡维地洛联合螺内酯治疗难治性高血压疗效好,值得临床推广。     

卡维地洛联合辛伐他汀治疗慢性心力衰竭的临床观察

目的：探讨卡维地洛联合辛伐他汀治疗慢性心力衰竭的临床效果。方法：选择确诊为慢性心力衰竭的住院患者160例,随机均分为对照组和观察组,对照组给予常规治疗,观察给予卡维地洛联合辛伐他汀治疗,2个月后检测血总胆固醇（TC）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、三酰甘油（TG）及心功能检查。结果：经2个月治疗后,对照组和观察组的血TC、LDL、HDL、TG比较,差异均有统计学意义（P〈0.05）;心功能改善在显效与无效方面,差异有统计学意义（P〈0.01）。结论：卡维地洛联合辛伐他汀治疗慢性心力衰竭能有效控制疾病,改善预后,临床效果肯定。