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RIFAXIMIN


ACCESSION NB: DB01220 (APRD01218)


TYPE: small molecule


GROUP: approved


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 is used to treat diarrhea caused by E. coli.

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Anti-Infective Agents Gastrointestinal Agents

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

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.

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.

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

AFECTED ORGANISMS:
Enteric bacteria and other eubacteria