Breckenridge Alasdair
Medicine and Healthcare Products Regulatory Agency, London.
Clin Med (Lond). 2006 Jul-Aug;6(4):393-7. doi: 10.7861/clinmedicine.6-4-393.
The lessons that the physician William Withering learned from his studies of digitalis are still relevant today. This paper highlights four of these lessons and updates them using the tools of clinical pharmacology and pharmacoepidemiology. First, Withering learned that failure to prepare digitalis from the foxglove in a standard manner resulted in a product with unpredictable clinical effects. Preparation of medicines from plants since then has not followed similar good practice and medicines have often not been granted marketing authorisation because of variability in their quality. Second, differences in the response to digitalis were noted by Withering, but he had little idea of their basis. Clinical pharmacology has shown that for drugs such as digitalis differences are caused by variability both in receptor sensitivity and in drug disposition. Third, the dose-response characteristics of digitalis were well known to Withering. Modern techniques of measuring response, such as the use of biomarkers, have made such studies easier, although clinical observations remain the gold standard. Fourth, Withering documented many of the adverse effects of digitalis. The use of various modern databases has facilitated the analysis of clinical toxicology and thus of risk-benefit profiles.
医生威廉·威瑟林从其对洋地黄的研究中学到的经验教训如今仍然适用。本文着重介绍其中四条经验教训，并运用临床药理学和药物流行病学工具对其进行更新。首先，威瑟林了解到，若不以标准方式从毛地黄中制备洋地黄，得到的产品临床效果将不可预测。从那时起，植物药的制备就未遵循类似的良好规范，而且由于质量参差不齐，药物往往未获上市许可。其次，威瑟林注意到对洋地黄的反应存在差异，但他对其原因知之甚少。临床药理学表明，对于洋地黄这类药物，差异是由受体敏感性和药物处置的变异性共同导致的。第三，威瑟林熟知洋地黄的剂量反应特性。尽管临床观察仍是金标准，但诸如使用生物标志物等现代测量反应的技术使此类研究变得更加容易。第四，威瑟林记录了洋地黄的许多不良反应。各种现代数据库的使用促进了临床毒理学分析，进而有助于分析风险效益概况。
