Investigational Drug Details
| Drug ID: | D304 |
| Drug Name: | Rifaximin |
| Synonyms: | Rifamycin L 105; Rifamycin L 105SV; Rifaxidin; Rifaximin |
| Type: | Chemical drug |
| DrugBank ID: | DB01220 |
| DrugBank Description: | Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, meaning that the drug will not pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. It has multiple indications and is used in treatment of traveller's diarrhea caused by E. coli; reduction in risk of overt hepatic encephalopathy recurrence; as well as diarrhea-predominant irritable bowel syndrome (IBS-D) in adult women and men. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals. |
| PubChem ID: | 6436173 |
| CasNo: | 80621-81-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O=C1c2c3c4c(n5c(n4)cc(cc5)C)c4c(c3c(c(c2O[C@]1(C)O/C=C/[C@H](OC)[C@@H](C)[C@@H](OC(=O)C)[C@H](C)[C@H](O)[C@H](C)[C@H]([C@H](/C=C/C=C(\C(=O)N4)/C)C)O)C)O)O |
| Structure: |
|
| InChiKey: | NZCRJKRKKOLAOJ-XRCRFVBUSA-N |
| Molecular Weight: | 785.891 |
| DrugBank Targets: | DNA-directed RNA polymerase subunit beta inhibitor; Nuclear receptor subfamily 1 group I member 2 agonist |
| DrugBank MoA: | Rifaximin acts by inhibiting RNA synthesis in susceptible bacteria by binding to the beta-subunit of bacterial deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase enzyme. This binding blocks translocation, which stops transcription. |
| DrugBank Pharmacology: | Rifaximin is a structural analog of rifampin and a non-systemic, gastrointestinal site-specific antibiotic. This non-systemic property of the drug is due to the addition of a pyridoimidazole ring, which renders it non-absorbable. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis and contributes to restore intestinal microflora imbalance. Other studies have also shown rifaximin to be an pregnane X receptor (PXR) activator. As PXR is responsible for inhibiting the proinflammatory transcription factor NF-kappa B (NF-κB) and is inhibited in inflammatory bowel disease (IBD), rifaximin was proven to be effective for the treatment of IBS-D. |
| DrugBank Indication: | Rifaximin has multiple indications by the FDA: for the treatment of patients (≥12 years of age) with traveller's diarrhea caused by noninvasive strains of Escherichia coli; for the reduction of overt hepatic encephalopathy recurrence in patients ≥18 years of age; and in May 2015 it was approved for irritable bowel syndrome with diarrhea (IBS-D) treatment in adult men and women. |
| Targets: | NR1I2 agonist |
| Therapeutic Category: | Antibiotic drug |
| Clinical Trial Progress: | Clinical trial on-going (IRCT20220104053626N1) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0147 | NCT01355575 | Phase 4 | Terminated | Has Results | May 2011 | October 28, 2020 | Details |
| L0194 | NCT02009592 | Not applicable | Completed | No Results Available | June 2013 | May 16, 2014 | Details |
| L0372 | IRCT20220104053626N1 | Phase 1/Phase 2 | Not Recruiting | No Results Available | 11/01/2022 | 7 February 2022 | Details |
| L0673 | EUCTR2010-021515-17-GB | Not applicable | Not Recruiting | No Results Available | 08/10/2010 | 5 November 2012 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A06752 | 32759852 | Int J Mol Sci | Effective Combination Therapy of Angiotensin-II Receptor Blocker and Rifaximin for Hepatic Fibrosis in Rat Model of Nonalcoholic Steatohepatitis. | Details |
| A07485 | 32476788 | World J Gastroenterol | Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care. | Details |
| A07754 | 32363684 | Aliment Pharmacol Ther | Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis. | Details |
| A08189 | 32213035 | United European Gastroenterol J | Clinical management of type C hepatic encephalopathy. | Details |
| A09183 | 31845776 | Am Fam Physician | Cirrhosis: Diagnosis and Management. | Details |
| A13186 | 30096092 | Eur J Gastroenterol Hepatol | Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot. | Details |
| A16387 | 28425154 | Hepatol Res | Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study. | Details |
| A17570 | 27741171 | J Clin Gastroenterol | Gut Microbiota and the Liver: A Tale of 2 Cities: A Narrative View in 2 Acts. | Details |
| A20291 | 26043290 | Eur J Gastroenterol Hepatol | Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. | Details |
| A43276 | 32087105 | Am J Med | A Confusing Picture: Refractory Encephalopathy Complicating Nonalcoholic Steatohepatitis. | Details |
| A45878 | 22230269 | Am Fam Physician | Cirrhosis: diagnosis, management, and prevention. | Details |
| A46705 | 16361039 | Clin Gastroenterol Hepatol | GIH clinical research update: 2004-2005. | Details |
| A48685 | 31509430 | Am J Physiol Gastrointest Liver Physiol | Rifaximin prevents ethanol-induced liver injury in obese KK-Ay mice through modulation of small intestinal microbiota signature. | Details |
| A49481 | 35740285 | Biomedicines | Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation. | Details |
| A50263 | 35450049 | Front Pharmacol | Rifaximin Ameliorates Non-alcoholic Steatohepatitis in Mice Through Regulating gut Microbiome-Related Bile Acids. | Details |
| A50797 | 35262903 | Dig Dis Sci | Incidence of, Risk Factors for, and Outcomes After Ascites in a Population-Based Cohort of Older Americans. | Details |
| A51428 | 35514019 | Dig Liver Dis | Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet-induced rat steatohepatitis. | Details |
| A52470 | 26618922 | Aliment Pharmacol Ther | Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis. | Details |