Absorption

Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms.

FLAGYL 375 capsules have been shown to have a rate and extent of absorption similar to metronidazole tablets (FLAGYL) and were bioequivalent at an equal single dose of 750 mg. In a study conducted with 23 adult, healthy, female volunteers, oral administration of two 375 mg FLAGYL capsules under fasted conditions produced a mean (±1 SD) peak plasma concentration (Cmax) of 21.4 (±2.8) mcg/mL with a mean Tmax of 1.6 (± 0.7) hours and a mean area under the plasma concentration-time curve (AUC) of 223 (±44) mcg∙hr/mL. In the same study, three 250 mg FLAGYL tablets produced a mean Cmax of 20.4 (± 3.8) mcg/mL with a mean Tmax of 1.4 (± 0.4) hours and a mean AUC of 218 (± 50) mcg∙hr/mL.

Administration of FLAGYL 375 capsules with food does not affect the extent of absorption of metronidazole; however, the presence of food results in a lower Cmax and a delayed Tmax compared to fasted conditions. In a study of 14 healthy, adult, female volunteers, administration of FLAGYL 375 capsules under fasting conditions produced a mean Cmax of 10.9 (± 1.5) mcg/mL, a mean Tmax of 1.5 (± 1.4) hours, and a mean AUC of 110 (± 34) mcg∙hr/mL compared to a mean Cmax of 8.6 (± 1.6) mcg/mL, a mean Tmax of 4.2 (± 1.7) hours, and a mean AUC of 99 (± 14) mcg∙hr/mL under fed conditions.

Distribution

Metronidazole is the major component appearing in the plasma, with lesser quantities of metabolites also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.

Metabolism/Excretion

The major route of elimination of metronidazole and its metabolites is via the urine (60% to 80% of the dose), with fecal excretion accounting for 6% to 15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(ß-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid] and glucuronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Both the parent compound and the hydroxyl metabolite possess in vitro antimicrobial activity against most strains of anaerobic bacteria and in vitro trichomonacidal activity.

Renal clearance of metronidazole is approximately 10 mL/min/1.73 m2. The average elimination half-life of metronidazole in healthy subjects is eight hours.