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Experimental and Clinical Pharmacology of Rifaximin, a Gastrointestinal Selective Antibiotic

Scarpignato C. · Pelosini I.

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Laboratory of Clinical Pharmacology, Department of Human Anatomy, Pharmacology and Forensic Sciences, School of Medicine and Dentistry, University of Parma, Parma, Italy

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Digestion 2006;73:13–27

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 27, 2006
Issue release date: February 2006

Number of Print Pages: 15
Number of Figures: 6
Number of Tables: 7

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: https://www.karger.com/DIG

Abstract

Rifaximin (4-deoxy-4′-methylpyrido[1′,2′-1,2]imidazo [5,4-c]rifamycin SV) is a product of synthesis experiments designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal (GI) absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a non-systemic antibiotic with a broad spectrum of antibacterial action covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually non-absorbed, its bioavailability within the GI tract is rather high with intraluminal and fecal drug concentrations that largely exceed the minimum inhibitory concentration values observed in vitro against a wide range of pathogenic organisms. The GI tract represents therefore the primary therapeutic target and GI infections the main indication. This antibiotic has therefore little value outside the enteric area and this will minimize both antimicrobial resistance and systemic adverse events. Indeed, the drug proved to be safe in all patient populations, including young children. The appreciation of the pathogenic role of gut bacteria in several organic and functional GI diseases has increasingly broadened its clinical use, which is now extended to hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease.

© 2006 S. Karger AG, Basel



 

Note Added in Proof


Note Added in Proof A recent prospective open label study [110] did confirm the effectiveness of rifaximin in controlling cryptosporidial diarrhea in patients with AIDS. The administration of this rifamycin derivative (400 mg b.i.d.) was associated with a rapid (within 1 week) and durable symptomatic control and eradication of the microorganism despite profound immunosuppression (CD4 count <50/mm3) in the majority of patients. In addition, an interesting case report [111] described long-lasting albeit intermittent abdominal pain and diarrhea in a patient with kidney-pancreas transplant on immunosuppressive therapy, which proved to be due to Cryptosporidium parvum infection. After the diagnosis, high dose (600 mg thrice daily) rifaximin treatment achieved complete symptom resolution within 1 week. Recent in vitro [112] and in vivo [113] studies, presented at the last Annual Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, D.C., did confirm the activity of rifaximin against C. difficile. In an experimental model of C. difficile-associated diarrhea (CDAD) [113] the efficacy of the rifamycin derivative was comparable to that of vancomycin. However, after stopping antibiotic treatment, 75% of the vancomycin-treated animals developed recurrent infection while none of the rifaximin-treated ones relapsed. These results suggest that rifaximin may be superior to vancomycin for the eradication of C. difficile infection. Since recurrent CDAD is a common clinical problem, specifically designed clinical trials are worthwhile to confirm this hypothesis.


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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 27, 2006
Issue release date: February 2006

Number of Print Pages: 15
Number of Figures: 6
Number of Tables: 7

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: https://www.karger.com/DIG


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