Table 1.
Evidence of clinical efficacy predicted by colonic transit as measured by scintigraphy
| Drug class | Pharmacodynamics (intestine or colon) | Clinical efficacy: phase IIB or II studies | Reference |
|---|---|---|---|
| 5-HT3-antagonist, alosetron | 1 mg b.i.d. delayed the rapid colonic transit in IBS-D | IIB, III studies in thousands of patients with non-IBS-C or IBS-D showed adequate relief of pain and discomfort of IBS, bowel dysfunction (including diarrhea), and urgency | 10 |
| 5-HT4-agonist, tegaserod | 2 mg b.i.d. accelerated SB transit and colonic transit in healthy persons and in patients with IBS-C (without evacuation disorder) | IIB, III studies in several thousands of patients with IBS-C and CC showed relief of pain and discomfort of IBS and bowel dysfunction | 11 |
| 5-HT4-agonist, prucalopride | Increased SB and colon motility and transit in healthy controls and in patients with CC | IIB and III in thousands of patients with CC showed improvement in BM frequency and satisfaction with bowel function | 12,13 |
| 5-HT4-agonist, velusetrag | Caused dose-related increases in SB and colon transit in healthy controls | IIB dose-ranging study in 401 patients with CC showed increased in BM frequency and proportion, with adequate relief | 14,15 |
| Bisacodyl | Accelerated colon transit in healthy controls | Showed relief of constipation after acute administration | 16,17 |
| Recombinant human neurotrophin (NT)-3 | NT-3 accelerated colonic transit in patients with CC | NT-3, administered TTW, increased stool frequency, enhanced colon transit, and improved symptoms of CC | 18,19 |
| C1–C2 channel activator, lubiprostone | Accelerated SB and colonic transit in healthy controls | Two phase III trials in several hundred patients with CC and IBS-C: efficacious in relief of pain and bowel dysfunction | 20–24 |
| Guanylate cyclase-C agonist, linaclotide | Accelerated AC transit and altered bowel function in 36 female patients with IBS-C | IIA and IIB studies in patients with CC or IBS-C showed increased BM frequency and relief from bloating and abdominal discomfort | 25,26 |
| κ-Opioid agonist, asimadoline | Showed no significant effect on colonic transit in healthy volunteers | On-demand dosing not effective in reducing severity of abdominal pain in 100 patients with IBS; IIB dose-ranging study on 596 patients with IBS: post hoc subgroup analysis showed benefit in average moderate pain in patients with IBS-D and IBS-Alt | 27–29 |
| CCK1-antagonist, dexloxiglumide | Showed slower AC emptying with no effect on overall colonic transit in patients with IBS-C | Two initial II B or III trials: not efficacious in patients with IBS-C; a randomized withdrawal design trial showed longer time to loss of therapeutic response, longer for dexloxiglumide | 30–32 |
| CRH1-antagonist, pexacerfont | Showed no effect on colonic transit and bowel function in patients with IBS-D | One phase IIB study showed that GW876008 showed no significant difference from placebo in the global improvement scale, daily self-assessment of IBS pain/discomfort, and individual lower GI symptoms | 33,34 |
| β3-Adrenergic agonist, solabegron | Showed no significant effect on GI or colonic transit | One phase IIB study showed no significant change in bowel symptoms, although there was adequate relief of IBS pain and discomfort | 35,36 |
AC, ascending colon; BM, bowel movement; Cl–C2, chloride channel type 2; CC, chronic constipation; CCK, cholecystokinin; CRH, corticotropin-releasing hormone; GI, gastrointestinal; 5-HT, 5-hydroxytryptamine; IBS, irritable bowel syndrome; IBS-Alt, alternating IBS; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; SB, small bowel; TTW, three times per week.