Table 3.
Examples of approved medications or combination probiotics for which pharmacogenomic measurements predicted clinical efficacy based on phase IIB and III trials (adapted from ref.35).
| Drug Class | Pharmacodynamics (intestine or colon) | Clinical Efficacy: Phase IIB or III Studies |
|---|---|---|
| 5-HT3-antagonist, alosetron | 1 mg BID delayed colonic transit diarrhea in IBS-D | IIB, III studies in thousands of patients with non-C-IBS or D-IBS adequate relief of pain and discomfort of IBS, bowel dysfunction (including diarrhea) and urgency |
| 5-HT4-agonist, Prucalopride | Increases SB, colon transit in healthy and patients with CC | IIB and III in CC (thousands of patients): BM frequency and satisfaction with bowel function both improved |
| Bisacodyl | Accelerates colon transit in healthy | Relief of constipation after acute administration and CC |
| Cl-C2 channel activator, lubiprostone | Accelerates SB and colonic transit in healthy controls | Several phase III in several hundred CC and IBS-C patients: efficacious in relief of pain and bowel dysfunction |
| Guanylate cyclase-C agonist, linaclotide | Accelerated AC transit and induced looser bowel function in 36 women with IBS-C | Several IIA, IIB and III studies in CC or C-IBS (several hundred) patients: increased BM frequency, relief of bloating, and abdominal discomfort |
| Ileal bile acid transport inhibitor, Elobixibat | Accelerates colonic transit and loosens stool consistency in functional constipation patients | Phase IIB and III studies showed improved stool frequency, and improved constipation-related symptoms in idiopathic CC |
| VSL-3 combination probiotic | Retards colonic transit in IBS-D, improves flatulence and bloating in IBS-D | Meta-analyses demonstrate symptom relief of multiple symptoms in IBS: global IBS, abdominal pain, bloating, and flatulence scores |
AC: ascending colon; BID: twice a day; BM: bowel movements; CC: chronic constipation; Cl−C2: chloride channel type 2; 5-HT: 5-hydroxytryptamine; IBS: irritable bowel syndrome; IBS-C: Constipation-predominant IBS; IBS-D: Diarrhea-predominant IBS; SB: small bowel