Weihrauch T R, Demol P
Department of Medicine, Pharmaceutical Research Center, Bayer AG, Wuppertal, FRG.
Z Gastroenterol. 1989 Aug;27(8):438-43.
Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.
已经进行了大量临床研究以确定药物在胃肠疾病中的疗效和安全性。然而，在这些研究中，只有少数（如果有的话）涉及了最佳剂量和给药方案的基本原理。充分且严格对照的剂量探索研究在新药的临床评估和新适应症的评价中起着关键作用。借此，可以评估从最小有效剂量到最大有效且耐受性良好的剂量范围，从而确定最佳剂量范围和给药方案。如果有对预期治疗效果具有高预测性的方法，例如胃酸分泌的测量及其被药物抑制的情况，那么在健康志愿者中也可以在胃肠道进行有意义的药效学研究。胃肠病学中的剂量探索研究可以从两个主要方面进行：第一，评估化合物对胃肠道的药效学和治疗效果（例如抗溃疡药物）。第二，评估药物对胃肠道的副作用（例如非甾体抗炎药对胃黏膜的损伤）。对于胃肠治疗新药的评估，有许多方法可以提供准确且可重复的数据。虽然十多年前就已经使用这些方法进行了仔细的临床药理学剂量反应研究，但令人惊讶的是，治疗剂量探索研究直到过去几年才出现。出于科学和伦理原因，需要进行更多确定最佳治疗剂量的试验。
