Sa1389 The Safety, Tolerability, and Pharmacokinetics of DA-6886, a Novel Serotonin 5-Hydroxytryptamine4 Receptor Agonist, in Healthy Subjects

descending (D) and sigmoid colon (S)] and the rectum (R) were measured. The stool and/ or gas distribution was evaluated using the following parameters: 1) Constipation index (CI)summing up the transverse diameter of each of the 5 segments according to the following formula [A+T+D+S+R / 5]; 2) Left/Right ratio (L/R)calculated from the following formula [(D+S) / (A+T)]. Colon transit time (CTT) was also assessed using radio opaque markers according to the established method by Metcalf, et al. First, patients were treated by either fiber or osmotic laxatives for 2 weeks. When constipation had not improved despite 2 weeks of treatment, stimulant laxatives were prescribed and followed for additional 2 weeks. Results: There was a significantly correlation between CI and CTT (r=0.75, p<0.01) (Fig). CI was significantly higher in CC patients than those with healthy subjects (p<0.05). According to their clinical courses, patients were divided into 3 groups: responder to either fiber or osmotic laxatives (group A), responder to stimulant laxatives (group B), and nonresponder (group C). CI was significantly lower in group A compared with both group B and C (p<0.05), and ROC curve analysis gave a cutoff value for CI of 19.7 for prediction of unfavorable outcomes of either fiber or osmotic laxatives (p<0.05), while L/R was significantly lower in group C compared with group B (p<0.05), and ROC curve analysis gave a cutoff value for L/R of 0.5 for prediction of non-responder of stimulant laxatives (p<0.05). Conclusions: Our data show that the stool and/or gas distribution evaluated by the US becomes an indirect indicator for CTT, and parameters evaluated by the US are associated with responsiveness to medical therapy for CC patients. These findings may assist physicians in predicting the unfavorable outcomes to medical therapies without side effects for this patient population.