Xifaxan Mechanism of Action

Pharmacotherapeutic Group: Intestinal anti-infective agents, antibiotics. ATC Code: A07AA11.
Pharmacology: Pharmacodynamics: Mode of Action: Rifaximin is an antibacterial agent of the rifamycin class that binds irreversibly to the β sub-unit of the bacterial enzyme DNA-dependent RNA polymerase and consequently inhibits bacterial RNA synthesis.
Mechanism of Resistance: The main mechanism of acquiring resistance to rifaximin appears to involve a mutation in the rpoB gene encoding the bacterial RNA polymerase.
Susceptibility: Rifaximin is a non-absorbed antibacterial agent. In vitro susceptibility testing cannot be used to reliably establish susceptibility or resistance of bacteria to rifaximin. There are currently insufficient data  available to support the setting of a clinical break point for susceptibility testing.
Pharmacokinetics: Absorption: Pharmacokinetic studies in rats, dogs and humans demonstrated that after oral administration, rifaximin in the polymorph α form is virtually not absorbed (<1%). Following the administration of therapeutic doses of rifaximin in healthy volunteers and patients with damaged intestinal mucosa (inflammatory bowel disease), plasma levels are negligible (<10 ng/mL). Systemic absorption of rifaximin is increased but not by a clinically relevant extent by administration within 30 min of a high-fat breakfast.
Elimination: The urinary recovery of rifaximin does not exceed 0.4% of the administered dose.
Special Populations: No clinical data are available on the use of rifaximin in patients with impaired renal function.
In patients with hepatic encephalopathy, mean peak plasma concentrations of 13.5 ng/mL rifaximin were detected after administration of 800 mg rifaximin 3 times daily for 7 days. Less than 0.1% of the administered dose was recovered after 7 days. Because of the limited systemic absorption of rifaximin, no specific dosing adjustments are recommended for patients with hepatic insufficiency.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity and genotoxicity. Morphological alterations have been observed in the foetuses of rifaximin orally administered rats and rabbits.