Normix Mechanism of Action

Pharmacotherapeutic group: Gastrointestinal Antibacterial.
Pharmacology: Rifaximin is a non-systemic antibiotic with a broad spectrum of antibacterial action due mainly to the inhibition of RNA-synthesis by binding to the β-subunit of the DNA-dependent RNA polymerase enzyme of both Gram-positive and Gram-negative bacteria. The characteristics of rifampin, in its polymorphic form α (alpha) is negligible adsorption (less than 1%) from the gastrointestinal tract; therefore, it is an agent with local antimicrobial activity at intestinal level against both pathogens and in clinical conditions where it is useful in reducing the endogenous intestinal bacterial load.
Bioavailability and Pharmacokinetics: Rifaximin absorption after oral administration is virtually nil (less than 1%), according to pharmacokinetic studies carried out on rats, dogs and in man.
Plasma levels are negligible (less than 10 ng/mL in almost all cases) following the administration of therapeutic doses of rifaximin in both healthy volunteers and Inflammatory Bowel Disease patients with damaged intestinal mucosa.
The urinary recovery of rifaximin does not exceed 0.4% of administered dose.
Virtually all orally administered rifaximin is available in the intestinal tract where it reaches very high concentrations (fecal concentrations of 4,000-8,000 µg/g are reached after 3 days of therapy with daily doses of 800 mg).
Systemic absorption of rifaximin was low in both the fasting state and when administered within 30 minutes of high-fat breakfast.
Comparative pharmacokinetic studies have shown that polymorphic forms of Rifaximin different from polymorphic form α were significantly absorbed.
Special Populations: No clinical data are available on the use of Rifaximin in patients with impaired renal function. However since the urinary recovery of Rifaximin does not exceed 0.4% of the administered dose in healthy volunteers, no dosage adjustment is necessary in patients with renal insufficiency.
In patients with hepatic encephalopathy Rifaximin mean peak rifaximin plasma concentrations of 13.5 ng/mL were detected in hepatic encephalopathy patients administered rifaximin 800 mg three times daily for 7 days/less than 0.1% 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.