Identification

Name
Rifaximin
Accession Number
DB01220  (APRD01218)
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
Synonyms
  • Rifamycin L 105
  • Rifamycin L 105SV
  • Rifaxidin
  • Rifaximin
  • Rifaximina
  • Rifaximine
  • Rifaximinum
  • Rifaximinun
  • Xifaxsan
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XifaxanTablet200 mg/1OralDispensing Solutions, Inc.2004-07-25Not applicableUs68258 110720180907 15195 ujtqrz
XifaxanTablet550 mg/1OralSalix Pharmaceuticals, Inc.2010-05-01Not applicableUs
XifaxanTablet200 mg/1OralA-S Medication Solutions2004-07-252017-07-31Us
XifaxanTablet200 mg/1OralAvera McKennan Hospital2015-05-07Not applicableUs
XifaxanTablet550 mg/1OralPhysicians Total Care, Inc.2010-08-19Not applicableUs65649 0303 02 nlmimage10 ca3ee557
XifaxanTablet200 mg/1OralSalix Pharmaceuticals, Inc.2004-07-25Not applicableUs
XifaxanTablet550 mg/1OralCardinal Health2010-05-01Not applicableUs
XifaxanTablet200 mg/1OralCarilion Materials Management2004-07-25Not applicableUs68151 498020180907 15195 ro9itf
XifaxanTablet200 mg/1OralPhysicians Total Care, Inc.2008-12-14Not applicableUs65649 0301 03 nlmimage10 951dcafe
XifaxanTablet550 mg/1OralSalix Pharmaceuticals, Inc2004-07-252009-06-24Us
International/Other Brands
Normix / Rifacol / Xifaxsan
Categories
UNII
L36O5T016N
CAS number
80621-81-4
Weight
Average: 785.8785
Monoisotopic: 785.352359489
Chemical Formula
C43H51N3O11
InChI Key
NZCRJKRKKOLAOJ-XRCRFVBUSA-N
InChI
InChI=1S/C43H51N3O11/c1-19-14-16-46-28(18-19)44-32-29-30-37(50)25(7)40-31(29)41(52)43(9,57-40)55-17-15-27(54-10)22(4)39(56-26(8)47)24(6)36(49)23(5)35(48)20(2)12-11-13-21(3)42(53)45-33(34(32)46)38(30)51/h11-18,20,22-24,27,35-36,39,48-51H,1-10H3,(H,45,53)/b12-11+,17-15+,21-13-/t20-,22+,23+,24+,27-,35-,36+,39+,43-/m0/s1
IUPAC Name
(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1⁴,⁷.0⁵,³⁵.0²⁶,³⁴.0²⁷,³²]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34),28,30,32-undecaen-13-yl acetate
SMILES
CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C)C(O)=C4C(O)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C1=C(N=C5C=C(C)C=CN15)C4=C3C2=O

Pharmacology

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.

Associated Conditions
Pharmacodynamics

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.

Mechanism of action

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 results in the blockage of the translocation step that normally follows the formation of the first phosphodiester bond, which occurs in the transcription process.

TargetActionsOrganism
ADNA-directed RNA polymerase subunit beta
inhibitor
Escherichia coli (strain K12)
NNuclear receptor subfamily 1 group I member 2
agonist
Human
Absorption

Low absorption in both the fasting state and when administered within 30 minutes of a high-fat breakfast.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

In vitro drug interactions studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/mL, did not inhibit human hepatic cytochrome P450 isoenzymes: 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4. In an in vitro hepa-tocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4), an isoenzyme which rifampin is known to induce.

Route of elimination

In a mass balance study, after administration of 400 mg 14C-rifaximin orally to healthy volunteers, of the 96.94% total recovery, 96.62% of the administered radioactivity was recovered in feces almost exclusively as the unchanged drug and 0.32% was recovered in urine mostly as metabolites with 0.03% as the unchanged drug.Rifaximin accounted for 18% of radioactivity in plasma. This suggests that the absorbed rifaximin undergoes metabolism with minimal renal excretion of the unchanged drug

Half life

Approximately 6 hours.

Clearance
Not Available
Toxicity

LD50 > 2 g/kg (orally, in rats)

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2-mercaptobenzothiazoleThe serum concentration of Rifaximin can be increased when it is combined with 2-mercaptobenzothiazole.
AbemaciclibThe serum concentration of Rifaximin can be increased when it is combined with Abemaciclib.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Rifaximin.
AcetaminophenThe serum concentration of Rifaximin can be increased when it is combined with Acetaminophen.
AcetazolamideThe metabolism of Rifaximin can be decreased when combined with Acetazolamide.
AfatinibThe serum concentration of Rifaximin can be increased when it is combined with Afatinib.
AgmatineThe metabolism of Agmatine can be increased when combined with Rifaximin.
AlbendazoleThe serum concentration of Rifaximin can be increased when it is combined with Albendazole.
AlclometasoneThe metabolism of Alclometasone can be increased when combined with Rifaximin.
AlectinibThe serum concentration of Rifaximin can be increased when it is combined with Alectinib.
Food Interactions
Not Available

References

Synthesis Reference

Giuseppe Viscomi, Manuela Campana, Dario Braga, Donatella Confortini, Vincenzo Cannata, Paolo Righi, Goffredo Rosini, "Polymorphic forms of rifaximin, processes for their production and uses thereof." U.S. Patent US20050272754, issued December 08, 2005.

US20050272754
General References
  1. Cottreau J, Baker SF, DuPont HL, Garey KW: Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections. Expert Rev Anti Infect Ther. 2010 Jul;8(7):747-60. doi: 10.1586/eri.10.58. [PubMed:20586560]
  2. Williams R, Bass N: Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety. Rev Gastroenterol Disord. 2005;5 Suppl 1:S10-8. [PubMed:15976747]
  3. Koo HL, DuPont HL: Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases. Curr Opin Gastroenterol. 2010 Jan;26(1):17-25. doi: 10.1097/MOG.0b013e328333dc8d. [PubMed:19881343]
  4. Pakyz AL: Rifaximin: a new treatment for travelers' diarrhea. Ann Pharmacother. 2005 Feb;39(2):284-9. Epub 2004 Dec 14. [PubMed:15598963]
  5. Jalan R: Rifaximin in hepatic encephalopathy: more than just a non-absorbable antibiotic? J Hepatol. 2010 Sep;53(3):580-2. doi: 10.1016/j.jhep.2010.05.002. Epub 2010 May 31. [PubMed:20561708]
  6. Lawrence KR, Klee JA: Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy. 2008 Aug;28(8):1019-32. doi: 10.1592/phco.28.8.1019. [PubMed:18657018]
  7. Layer P, Andresen V: Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of travellers' diarrhoea. Aliment Pharmacol Ther. 2010 Jun;31(11):1155-64. doi: 10.1111/j.1365-2036.2010.04296.x. Epub 2010 Mar 11. [PubMed:20331580]
  8. Ojetti V, Lauritano EC, Barbaro F, Migneco A, Ainora ME, Fontana L, Gabrielli M, Gasbarrini A: Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):675-82. doi: 10.1517/17425250902973695. [PubMed:19442033]
  9. Scarpignato C, Pelosini I: Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 Suppl 1:36-66. [PubMed:15855748]
  10. Gillis JC, Brogden RN: Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs. 1995 Mar;49(3):467-84. [PubMed:7774516]
  11. Koo HL, Dupont HL, Huang DB: The role of rifaximin in the treatment and chemoprophylaxis of travelers' diarrhea. Ther Clin Risk Manag. 2009;5:841-8. Epub 2009 Nov 2. [PubMed:19898648]
  12. DuPont HL: Systematic review: prevention of travellers' diarrhoea. Aliment Pharmacol Ther. 2008 May;27(9):741-51. doi: 10.1111/j.1365-2036.2008.03647.x. Epub 2008 Feb 14. [PubMed:18284650]
  13. Romero-Gomez M: Pharmacotherapy of hepatic encephalopathy in cirrhosis. Expert Opin Pharmacother. 2010 Jun;11(8):1317-27. doi: 10.1517/14656561003724721. [PubMed:20384539]
  14. Scarpignato C, Pelosini I: Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13-27. Epub 2006 Feb 8. [PubMed:16498249]
  15. Pimentel M: Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009 Mar;18(3):349-58. doi: 10.1517/13543780902780175 . [PubMed:19243285]
  16. Rifaximin Australian Public Assessment Report [File]
External Links
Human Metabolome Database
HMDB15351
KEGG Drug
D02554
PubChem Compound
6436173
PubChem Substance
46508705
ChemSpider
10482302
BindingDB
50347620
ChEBI
75246
ChEMBL
CHEMBL1617
Therapeutic Targets Database
DAP001006
PharmGKB
PA164752443
HET
RXM
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Rifaximin
ATC Codes
D06AX11 — RifaximinA07AA11 — Rifaximin
AHFS Codes
  • 08:12.28.30 — Rifamycins
PDB Entries
6bee
FDA label
Download (478 KB)
MSDS
Download (58.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentEnd Stage Renal Disease (ESRD)1
0RecruitingTreatmentMicrobial Colonization1
1CompletedNot AvailablePharmacokinetics1
1CompletedTreatmentMalignancies / Transplantation, Bone Marrow1
1CompletedTreatmentPrimary Sclerosing Cholangitis (PSC)1
1Unknown StatusTreatmentGulf War Syndrome1
1, 2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
1, 2CompletedTreatmentMinimal Hepatic Encephalopathy1
1, 2Not Yet RecruitingTreatmentParkinson's Disease (PD)1
1, 2RecruitingPreventionCirrhotic Patients Undergoing TIPS Placement1
1, 2RecruitingTreatmentCrohn's Disease (CD)1
2Active Not RecruitingTreatmentCrohn's Disease (CD)1
2Active Not RecruitingTreatmentHepatitis C Viral Infection1
2CompletedPreventionDiarrhea1
2CompletedPreventionLiver Cirrhosis1
2CompletedTreatmentCirrhoses, Liver1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2CompletedTreatmentIrritable Bowel Syndrome (IBS)2
2Enrolling by InvitationTreatmentAlcoholic Hepatitis (AH)1
2RecruitingTreatmentAdherent-invasive E. Coli / Crohn's Disease (CD)1
2RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
2RecruitingTreatmentIrritable Bowel Syndrome (IBS) / Visceral Hypersensitivity1
2RecruitingTreatmentMajor Liver Resection / Malignant Liver Disease1
2Unknown StatusTreatmentHepatic Encephalopathy1
2Unknown StatusTreatmentHepatic Encephalopathy / Hepatitis C Viral Infection / Liver Cirrhosis1
2WithdrawnTreatmentRosaceas1
2, 3CompletedTreatmentFunctional Dyspepsia1
2, 3CompletedTreatmentParkinson's Disease (PD) / Small Intestinal Bacterial Overgrowth1
2, 3RecruitingTreatmentFecal Microbiota Transplantation / Irritable Bowel Syndrome (IBS)1
2, 3RecruitingTreatmentIrritable Bowel Syndrome (IBS)1
2, 3RecruitingTreatmentLiver Cirrhosis / Portal Hypertension1
3Active Not RecruitingTreatmentRectal Carcinoma1
3CompletedPreventionDiarrhea2
3CompletedPreventionDiarrhoea1
3CompletedPreventionHepatic Encephalopathy2
3CompletedTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
3CompletedTreatmentClostridium Infections / Diarrhea1
3CompletedTreatmentDiarrhea1
3CompletedTreatmentDiarrhoea Predominant Irritable Bowel Syndrome1
3CompletedTreatmentLiver Cirrhosis1
3CompletedTreatmentNon-Constipation Irritable Bowel Syndrome2
3CompletedTreatmentParkinson's Disease (PD)1
3Not Yet RecruitingPreventionCrohn's Disease (CD)1
3Not Yet RecruitingTreatmentCollagenous Colitis1
3Not Yet RecruitingTreatmentSevere Alcoholic Hepatitis1
3RecruitingPreventionAscites / Liver Cirrhosis / Spontaneous Bacterial Peritonitis (SBP)1
3RecruitingPreventionCrohn's Disease (CD)1
3RecruitingTreatmentAscites / Liver Cirrhosis / Peritonitis1
3RecruitingTreatmentLiver Cirrhosis / Portal Hypertension1
3TerminatedTreatmentTravelers' Diarrhea1
3WithdrawnPreventionSpontaneous Bacterial Peritonitis (SBP)1
3WithdrawnTreatmentHepatic Encephalopathy1
4CompletedBasic ScienceAscites / Liver Cirrhosis1
4CompletedBasic ScienceCommon Variable Immunodeficiency (CVID)1
4CompletedPreventionHepatic Encephalopathy1
4CompletedTreatmentDiverticular disorders1
4CompletedTreatmentHepatic Encephalopathy / Liver Cirrhosis1
4CompletedTreatmentTravelers' Diarrhea1
4Not Yet RecruitingTreatmentCovert Hepatic Encephalopathy1
4RecruitingBasic ScienceDiarrhoea Predominant Irritable Bowel Syndrome1
4RecruitingPreventionChronic Kidney Disease (CKD)1
4RecruitingPreventionClostridium Difficile Infection (CDI)1
4RecruitingTreatmentHepatic Encephalopathy1
4RecruitingTreatmentIrritable Bowel Syndrome (IBS)1
4RecruitingTreatmentLiver Cirrhosis1
4TerminatedTreatmentHepatic Encephalopathy / Liver Cirrhosis / Portal Hypertension1
4TerminatedTreatmentNAFLD / Nonalcoholic Fatty Liver Disease / Nonalcoholic Steatohepatitis1
4Unknown StatusPreventionLiver Cirrhosis1
4Unknown StatusTreatmentLiver Cirrhosis / Renal Failure1
4WithdrawnPreventionHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
4WithdrawnTreatmentTravelers' Diarrhea1
Not AvailableActive Not RecruitingBasic ScienceChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableActive Not RecruitingPreventionFunctional Bowel Disorders / Reactive Arthritis / Travelers' Diarrhea1
Not AvailableCompletedNot AvailableTropical Enteropathy1
Not AvailableCompletedDiagnosticHepatic Encephalopathy / Liver Cirrhosis1
Not AvailableCompletedDiagnosticIntestinal FDG Uptake1
Not AvailableCompletedTreatmentAcute on Chronic Liver Failure With Hepatic Encephalopathy / Acute-On-Chronic Liver Failure1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / Diabetes Mellitus (DM)1
Not AvailableCompletedTreatmentChronic Abdominal Discomfort / Functional Dyspepsia / Small Intestinal Bacterial Overgrowth1
Not AvailableCompletedTreatmentChronic Abdominal Pain / Small Intestinal Bacterial Overgrowth1
Not AvailableCompletedTreatmentCirrhosis Related Parkinsonism / Hepatic/Cirrhosis Related Parkinsonism1
Not AvailableCompletedTreatmentConstipation-Predominant Irritable Bowel Syndrome1
Not AvailableCompletedTreatmentEsophageal and Gastric Varices / Hemorrhage, Gastrointestinal / Liver Cirrhosis1
Not AvailableCompletedTreatmentFatty Liver / Steatohepatitis1
Not AvailableCompletedTreatmentGluten Enteropathy1
Not AvailableCompletedTreatmentHepatic Encephalopathy2
Not AvailableCompletedTreatmentIBS1
Not AvailableCompletedTreatmentIrritable Bowel Syndrome (IBS) / Small Intestinal Bacterial Overgrowth1
Not AvailableCompletedTreatmentUlcerative Colitis (UC)1
Not AvailableNot Yet RecruitingTreatmentLiver Cirrhosis / Portal Vein Thrombosis1
Not AvailableRecruitingDiagnosticDumping Syndrome / Gastric Resection / Hypoglycemia / Oesophagectomy1
Not AvailableRecruitingPreventionEsophageal and Gastric Varices / Hemorrhage, Gastrointestinal / Liver Cirrhosis1
Not AvailableRecruitingTreatmentLiver Cirrhosis / Small Intestinal Bacterial Overgrowth1
Not AvailableRecruitingTreatmentRefractory Hepatic Encephalopathy1
Not AvailableTerminatedDiagnosticDigestive System Diseases / Gastrointestinal Diseases / Small Bowel Bacterial Overgrowth / Stomach Diseases1
Not AvailableTerminatedTreatmentAcute Watery Diarrhea / Dysentery/Febrile Diarrhea1
Not AvailableUnknown StatusNot AvailableSimple Diverticular Disease1
Not AvailableUnknown StatusTreatmentHepatopulmonary Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Diversified Healthcare Services Inc.
  • Patheon Inc.
  • Physicians Total Care Inc.
  • Salix Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral200 mg/1
TabletOral550 mg/1
TabletOral550 mg
Prices
Unit descriptionCostUnit
Xifaxan 550 mg tablet22.4USD tablet
Xifaxan 200 mg tablet8.97USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7928115No2009-07-242029-07-24Us
US8741904No2006-02-272026-02-27Us
US7612199No2004-06-192024-06-19Us
US8853231No2004-06-192024-06-19Us
US8158644No2004-06-192024-06-19Us
US8193196No2007-09-022027-09-02Us
US7906542No2005-06-012025-06-01Us
US8158781No2004-06-192024-06-19Us
US7045620No2004-06-192024-06-19Us
US8518949No2006-02-272026-02-27Us
US8835452No2004-06-192024-06-19Us
US7902206No2004-06-192024-06-19Us
US8829017No2009-07-242029-07-24Us
US8642573No2009-10-022029-10-02Us
US8969398No2009-10-022029-10-02Us
US8946252No2009-07-242029-07-24Us
US7915275No2005-02-232025-02-23Us
US8309569No2009-07-182029-07-18Us
US7718608No1999-08-112019-08-11Us
US7452857No1999-08-112019-08-11Us
US6861053No1999-08-112019-08-11Us
US7605240No1999-08-112019-08-11Us
US7935799No1999-08-112019-08-11Us
US9271968No2006-02-272026-02-27Us
US9421195No2010-03-102030-03-10Us
US9629828No2009-07-242029-07-24Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00738 mg/mLALOGPS
logP4.94ALOGPS
logP4.37ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)3.66ChemAxon
pKa (Strongest Basic)11.87ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area198.38 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity216.69 m3·mol-1ChemAxon
Polarizability82.26 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.646
Blood Brain Barrier-0.973
Caco-2 permeable-0.6301
P-glycoprotein substrateSubstrate0.6681
P-glycoprotein inhibitor INon-inhibitor0.6985
P-glycoprotein inhibitor IINon-inhibitor0.7134
Renal organic cation transporterNon-inhibitor0.9533
CYP450 2C9 substrateNon-substrate0.8256
CYP450 2D6 substrateNon-substrate0.8783
CYP450 3A4 substrateSubstrate0.5651
CYP450 1A2 substrateNon-inhibitor0.7129
CYP450 2C9 inhibitorNon-inhibitor0.7393
CYP450 2D6 inhibitorNon-inhibitor0.875
CYP450 2C19 inhibitorNon-inhibitor0.7684
CYP450 3A4 inhibitorNon-inhibitor0.8904
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7729
Ames testNon AMES toxic0.6276
CarcinogenicityNon-carcinogens0.9055
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6259 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.994
hERG inhibition (predictor II)Non-inhibitor0.721
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolactams
Sub Class
Not Available
Direct Parent
Macrolactams
Alternative Parents
Naphthofurans / Naphthols and derivatives / Benzimidazoles / Benzofurans / Coumarans / Imidazo[1,2-a]pyridines / Aryl alkyl ketones / Methylpyridines / Ketals / N-substituted imidazoles
show 14 more
Substituents
Macrolactam / Naphthofuran / 1-naphthol / Naphthalene / Benzimidazole / Benzofuran / Coumaran / Imidazo[1,2-a]pyridine / Aryl alkyl ketone / Aryl ketone
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
acetate ester, organic heterohexacyclic compound, lactam, semisynthetic derivative, macrocycle, cyclic ketal, rifamycin (CHEBI:75246)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ribonucleoside binding
Specific Function
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Gene Name
rpoB
Uniprot ID
P0A8V2
Uniprot Name
DNA-directed RNA polymerase subunit beta
Molecular Weight
150631.165 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Vitali B, Turroni S, Dal Piaz F, Candela M, Wasinger V, Brigidi P: Genetic and proteomic characterization of rifaximin resistance in Bifidobacterium infantis BI07. Res Microbiol. 2007 May;158(4):355-62. Epub 2007 Feb 22. [PubMed:17408927]
  4. Ojetti V, Lauritano EC, Barbaro F, Migneco A, Ainora ME, Fontana L, Gabrielli M, Gasbarrini A: Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):675-82. doi: 10.1517/17425250902973695. [PubMed:19442033]
  5. Koo HL, Dupont HL, Huang DB: The role of rifaximin in the treatment and chemoprophylaxis of travelers' diarrhea. Ther Clin Risk Manag. 2009;5:841-8. Epub 2009 Nov 2. [PubMed:19898648]
  6. Scarpignato C, Pelosini I: Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13-27. Epub 2006 Feb 8. [PubMed:16498249]
  7. Pimentel M: Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009 Mar;18(3):349-58. doi: 10.1517/13543780902780175 . [PubMed:19243285]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Cheng J, Shah YM, Ma X, Pang X, Tanaka T, Kodama T, Krausz KW, Gonzalez FJ: Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther. 2010 Oct;335(1):32-41. doi: 10.1124/jpet.110.170225. Epub 2010 Jul 13. [PubMed:20627999]
  2. Ma X, Shah YM, Guo GL, Wang T, Krausz KW, Idle JR, Gonzalez FJ: Rifaximin is a gut-specific human pregnane X receptor activator. J Pharmacol Exp Ther. 2007 Jul;322(1):391-8. Epub 2007 Apr 18. [PubMed:17442842]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  3. Hoffman JT, Hartig C, Sonbol E, Lang M: Probable interaction between warfarin and rifaximin in a patient treated for small intestine bacterial overgrowth. Ann Pharmacother. 2011 May;45(5):e25. doi: 10.1345/aph.1P578. Epub 2011 Apr 19. [PubMed:21505109]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Rana R, Chen Y, Ferguson SS, Kissling GE, Surapureddi S, Goldstein JA: Hepatocyte nuclear factor 4{alpha} regulates rifampicin-mediated induction of CYP2C genes in primary cultures of human hepatocytes. Drug Metab Dispos. 2010 Apr;38(4):591-9. doi: 10.1124/dmd.109.030387. Epub 2010 Jan 19. [PubMed:20086032]
  2. Edwards RJ, Price RJ, Watts PS, Renwick AB, Tredger JM, Boobis AR, Lake BG: Induction of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos. 2003 Mar;31(3):282-8. [PubMed:12584154]
  3. Rifaximin FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Agrawal A, Agarwal SK, Kaleekal T, Gupta YK: Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact. Indian J Nephrol. 2016 Sep;26(5):322-328. doi: 10.4103/0971-4065.176145. [PubMed:27795624]

Drug created on June 13, 2005 07:24 / Updated on October 15, 2018 04:36