Smith Julian C, Tarocco Giorgio, Merazzi Fabio, Salzmann Urs
Pharmaceutical Sciences, Aston University, Birmingham, UK.
Curr Med Res Opin. 2006 Apr;22(4):709-20. doi: 10.1185/030079906X96461.
Carvedilol is a comprehensive beta(1)-, beta(2)-, and alpha(1)-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.
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.
The generic products were subjected to four key tests: carvedilol content, tablet hardness, tablet dissolution and purity.
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.
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.
卡维地洛是一种全面的β₁、β₂和α₁肾上腺素能受体阻滞剂，由F. Hoffmann-La Roche Ltd.（罗氏公司）以Dilatrend品牌销售，葛兰素史克公司以Coreg品牌销售，用于治疗高血压、稳定型心绞痛、心肌梗死后左心室功能不全以及各种程度的症状性慢性心力衰竭。
在本报告中，根据欧洲药典和罗氏公司的规格，对Dilatrend 6.25毫克、12.5毫克和25毫克片剂以及从19个国家的20家制造商随机选取的35种卡维地洛仿制药的药学质量进行了评估。
对这些仿制药进行了四项关键测试：卡维地洛含量、片剂硬度、片剂溶出度和纯度。
所有三种Dilatrend规格均符合标准。至少17/35（48.6%）的仿制药不符合标准，原因如下：卡维地洛平均含量不正确（超出95 - 105%）——3种产品；杂质超标（> 0.3%）——1种产品；片剂硬度不正确（超出30 - 70牛顿）——11种产品；溶出度不足（30分钟内< 75%）——9种产品。7种产品（20%）两项测试不合格，通常是硬度和溶出度测试。
用药学性质不同且可能质量较差的仿制药逐剂量替代卡维地洛原制剂（Dilatrend），由于药代动力学或生物等效性的意外变化，可能会导致治疗效果改变，和/或因杂质导致耐受性改变。
