Pharmacokinetics

Absorption: The mean pharmacokinetic parameters of rifaximin in 14 healthy subjects after a single oral 400-mg dose given as 2 x 200 mg doses under fed and fasting conditions are summarized in Table 1.

Table 1 : Effect of Food on the Mean ± S.D. Pharmacokinetic Parameters Following a Single 400-mg Dose of Rifaximin (N = 14)

Rifaximin can be administered with or without food. Systemic absorption of rifaximin was low in both the fasting state and when administered within 30 minutes of a high-fat breakfast.

¹⁴C-Rifaximin was administered as a single dose to 4 healthy male subjects. The mean overall recovery of radioactivity in the urine and feces of 3 subjects during the 168 hours after administration was 96.94 ± 5.64% of the dose. Radioactivity was excreted almost exclusively in the feces (96.62 ± 5.67% of the dose), with only a small proportion of the dose (mean 0.32% of the dose) excreted in urine. Analysis of fecal extracts indicated that rifaximin was being excreted as unchanged drug. The amount of radioactivity in urine ( < 0.4% of the dose) suggests that rifaximin is poorly absorbed from the gastrointestinal tract and is almost exclusively and completely excreted in feces as unchanged drug. Mean rifaximin pharmacokinetic parameters were Cmax 4.3 ± 2.8 ng/mL and AUCt 19.5 ± 16.5 ng•h/mL with a median Tmax of 1.25 hours.

Systemic absorption of rifaximin (200 mg three times daily) was also evaluated in 13 subjects with shigellosis on Days 1 and 3 of a three-day course of treatment. Rifaximin concentrations and exposures were low and variable. There was no evidence of accumulation of rifaximin following repeated administration for 3 days (9 doses). Peak plasma rifaximin concentrations after 3 and 9 consecutive doses ranged from 0.81 to 3.4 ng/mL on Day 1 and 0.68 to 2.26 ng/mL on Day 3. Similarly, AUC0-last estimates were 6.95 ± 5.15 ng•h/mL on Day 1 and 7.83 ± 4.94 ng•h/mL on Day 3. Rifaximin is not suitable for treating systemic bacterial infections because less than 0.4% of the drug is absorbed after oral administration (see WARNINGS).

Distribution: Animal pharmacokinetic studies have demonstrated that 80% to 90% of orally administered rifaximin is concentrated in the gut with less than 0.2% in the liver and kidney, and less than 0.01% in other tissues. In adults with infectious diarrhea treated with rifaximin 800 mg daily for three days, concentrations of rifaximin in stools averaged ~8000 µg/g the day after treatment ended.

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 hepatocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4), an isoenzyme which rifampin is known to induce. Two clinical drug-drug interaction studies using midazolam and an oral contraceptive containing ethinyl estradiol and norgestimate demonstrated that rifaximin did not alter the pharmacokinetics of these drugs (see Drug-Drug Interactions).

Excretion: Rifaximin is excreted primarily in the feces. After oral administration of 400 mg ¹⁴C-rifaximin to healthy volunteers, approximately 97% of the dose was recovered in feces, almost entirely as unchanged drug, and 0.32% was recovered in the urine.

Special Populations

Bookmark this page: