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Experimental and Clinical Pharmacology of Rifaximin, a Gastrointestinal Selective Antibiotic

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.