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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2018-05-20 20:17:45 UTC
HMDB IDHMDB0015351
Secondary Accession Numbers
  • HMDB15351
Metabolite Identification
Common NameRifaximin
DescriptionRifaximin is only found in individuals that have used or taken this drug. It 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 is used to treat diarrhea caused by E. coli.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.
Structure
Thumb
Synonyms
ValueSource
4-Deoxy-4'-methylpyrido(1',2'-1,2)imidazo(5,4C)rifamycinMeSH
RedactivMeSH
RifaximinMeSH
XifaxanMeSH
Chemical FormulaC43H51N3O11
Average Molecular Weight785.891
Monoisotopic Molecular Weight785.352359474
IUPAC Name(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,23,36-pentahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6-oxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1⁴,⁷.0⁵,³⁵.0²⁶,³⁴.0²⁷,³²]heptatriaconta-1(35),2,4,9,19,21,23,25(36),26(34),28,30,32-dodecaen-13-yl acetate
Traditional Namexifaxsan
CAS Registry Number80621-81-4
SMILES
[H]\C1=C([H])\[C@]([H])(OC)[C@@]([H])(C)[C@@]([H])(OC(C)=O)[C@]([H])(C)[C@]([H])(O)[C@]([H])(C)[C@@]([H])(O)[C@@]([H])(C)\C([H])=C(\[H])/C(/[H])=C(C)\C(O)=NC2=C(O)C3=C(C4=C2N2C=CC(C)=CC2=N4)C2=C(O[C@](C)(O1)C2=O)C(C)=C3O
InChI Identifier
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
InChI KeyNZCRJKRKKOLAOJ-LGPAXTBISA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolactams
Sub ClassNot Available
Direct ParentMacrolactams
Alternative Parents
Substituents
  • Macrolactam
  • Naphthofuran
  • 1-naphthol
  • Naphthalene
  • Benzimidazole
  • Imidazo[1,2-a]pyridine
  • Coumaran
  • Benzofuran
  • Aryl alkyl ketone
  • Aryl ketone
  • Ketal
  • Phenol
  • Methylpyridine
  • Benzenoid
  • Pyridine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Acetate salt
  • Azole
  • Lactam
  • Secondary alcohol
  • Secondary carboxylic acid amide
  • Ketone
  • Carboxylic acid ester
  • Carboxamide group
  • Acetal
  • Carboxylic acid derivative
  • Oxacycle
  • Dialkyl ether
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Polyol
  • Monocarboxylic acid or derivatives
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organic oxide
  • Carbonyl group
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0074 g/LNot Available
LogP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0074 g/LALOGPS
logP5.14ALOGPS
logP4.79ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)-2ChemAxon
pKa (Strongest Basic)15.28ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area201.87 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity217.45 m³·mol⁻¹ChemAxon
Polarizability84.24 ųChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014r-0000000900-19cdae42a8f052959f6fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0kxr-0000000900-220873604573c9752f4dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-056r-0000000900-7b85571f844525173846View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0000000900-b188da8cf176294aecf4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-06ec-1000000900-54e6cb30802b467c99efView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-3000000900-fa581886bf5e0432cd5bView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01220 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01220 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID23975968
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound46783403
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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 ]
  2. Pakyz AL: Rifaximin: a new treatment for travelers' diarrhea. Ann Pharmacother. 2005 Feb;39(2):284-9. Epub 2004 Dec 14. [PubMed:15598963 ]
  3. Scarpignato C, Pelosini I: Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 Suppl 1:36-66. [PubMed:15855748 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  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. 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 ]
  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. 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 ]
  15. 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 ]

Enzymes

General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
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 and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular weight:
49761.2
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 ]