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药品详细

Rifaximin(利福昔明)

化学结构式图
中文名
利福昔明
英文名
Rifaximin
分子式
C43H51N3O11
化学名
(7S,11S,12R,13S,14R,15R,16R,17S,18S)-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[23.10.1.1^{4,7}.0^{5,35}.0^{26,34}.0^{27,32}]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34),28,30,32-undecaen-13-yl acetate
分子量
Average: 785.8785
Monoisotopic: 785.352359489
CAS号
80621-81-4
ATC分类
A07A 未知;D06A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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 is used to treat diarrhea caused by E. coli.

生产厂家
  • Salix pharmaceuticals inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  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. Pubmed
  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
  3. Koo HL, DuPont HL: Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases. Curr Opin Gastroenterol. 2010 Jan;26(1):17-25. Pubmed
  4. Pakyz AL: Rifaximin: a new treatment for travelers’ diarrhea. Ann Pharmacother. 2005 Feb;39(2):284-9. Epub 2004 Dec 14. Pubmed
  5. Jalan R: Rifaximin in hepatic encephalopathy: More than just a non-absorbable antibiotic? J Hepatol. 2010 May 31. Pubmed
  6. Lawrence KR, Klee JA: Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy. 2008 Aug;28(8):1019-32. Pubmed
  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. Epub 2010 Mar 11. Pubmed
  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. Pubmed
  9. Scarpignato C, Pelosini I: Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 Suppl 1:36-66. Pubmed
  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
  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
  12. DuPont HL: Systematic review: prevention of travellers’ diarrhoea. Aliment Pharmacol Ther. 2008 May;27(9):741-51. Epub 2008 Feb 14. Pubmed
  13. Romero-Gomez M: Pharmacotherapy of hepatic encephalopathy in cirrhosis. Expert Opin Pharmacother. 2010 Jun;11(8):1317-27. Pubmed
  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
  15. Pimentel M: Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009 Mar;18(3):349-58. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Ansamycins
  • Lactams
Substructures
  • Ansamycins
  • Carboxylic Acids and Derivatives
  • Benzofurans
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Naphthalenes
  • Acetates
  • Acetals and Derivatives
  • Phenols and Derivatives
  • Benzimidazoles
  • Amino Ketones
  • Ethers
  • Pyridines and Derivatives
  • Imidazopyridines
  • Benzene and Derivatives
  • Aminophenols and Derivatives
  • Methoxyphenols
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Lactams
  • Benzoyl Derivatives
  • Cyanamides
  • Alcohols and Polyols
  • Phenyl Esters
  • Anilines
  • Ketones
适应症
药理
Indication For the treatment of patients (≥12 years of age) with travelers' diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin is also designated an orphan drug by the Food and Drug Administration for the adjunctive treatment of hepatic encephalopathy to reduce blood ammonia concentrations and decrease severity of neurological manifestations.
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 may prove to be effective for the treatment of IBD.
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.
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
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 2.6 Not Available
Predicted Properties
Property Value Source
water solubility 7.38e-03 g/l ALOGPS
logP 4.94 ALOGPS
logP 4.37 ChemAxon
logS -5 ALOGPS
pKa (strongest acidic) 3.66 ChemAxon
pKa (strongest basic) 11.87 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 11 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 198.38 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 216.69 ChemAxon
polarizability 82.26 ChemAxon
药物相互作用
食物相互作用
Not Available

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