Challenges in drug development for functional gastrointestinal disorders. Part II: visceral pain.

There is a need to have predictive biomarkers to test novel experimental medicines in functional gastrointestinal disorders. The human pharmacodynamic models and biomarkers pertaining to two important conditions are reviewed in a two-part article: functional dyspepsia (part I) and visceral pain (part II). With visceral pain models, the large coefficient of variation in sensation end points in human studies precludes definitive conclusions such as go/no go decisions or dose selection for phase IIb or III studies, unless very large numbers of patients are evaluated in phase IIA pharmacodynamic studies. This renders such pharmacological studies ambitious, or unachievable in a timely fashion. Moreover, the results of tests and clinical trials should be interpreted with greater knowledge of the drug pharmacokinetics, including the influence of CYP metabolism and potential drug interactions. Thus, it is important to identify valid biomarkers of visceral pain for the assessment of treatment response in pharmacodynamic studies. In this second part of a two-part article, we shall discuss the special challenges in developing medications for visceral pain and the general importance of including pharmacokinetic and pharmacogenomic studies in drug development programmes.