Camilleri M, Talley N J
Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Neurogastroenterol Motil. 2004 Apr;16(2):135-42. doi: 10.1111/j.1365-2982.2004.00516.x.
Sensorimotor disorders of the stomach, small intestine and colon have a limited repertoire of clinical manifestations, and there is the potential for more than one mechanism to lead to symptoms. In many recent clinical trial programs of novel agents in neurogastroenterology, the emphasis has been primarily on symptom assessment of broad groups of patients identified by the Rome criteria. Drugs of potential value have fallen by the wayside with this approach. We propose the current paradigm is partly to blame; physiological testing should provide the basis for identifying more homogeneous populations and therapeutic targets within functional bowel disease, and this applies to the upper and lower gut. Here we summarize the evidence that certain biomarkers can, in a limited fashion, be used to predict the success of an experimental medicine in common disorders of gastrointestinal function, including the irritable bowel syndrome and functional dyspepsia. Although the current evidence is limited and is most convincingly demonstrated with examples of transit measurements (for loperamide, alosetron, tegaserod and piboserod), we perceive this paradigm that studies using validated and responsive biomarkers have an important role to play in drug development.
胃、小肠和结肠的感觉运动障碍临床表现有限，且可能有多种机制导致症状。在神经胃肠病学领域许多新型药物的近期临床试验项目中，重点主要放在对符合罗马标准的广大患者群体进行症状评估上。采用这种方法，具有潜在价值的药物就被忽视了。我们认为当前的模式应为此承担部分责任；生理测试应为在功能性肠病中识别更同质的人群和治疗靶点提供依据，这适用于上消化道和下消化道。在此，我们总结了相关证据，即某些生物标志物可在一定程度上用于预测实验性药物在常见胃肠功能障碍（包括肠易激综合征和功能性消化不良）中的疗效。尽管目前的证据有限，且在转运测量实例（如洛哌丁胺、阿洛司琼、替加色罗和匹莫色罗）中得到了最令人信服的证明，但我们认为使用经过验证且反应灵敏的生物标志物进行研究的这一模式在药物研发中可发挥重要作用。
