Pharmacologic Classification: Antibacterial/Antiprotozoal.
Pharmacology: Pharmacokinetics: Bioavailability: At least 80% of metronidazole is absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations of approximately 5 and 10 mcg/mL are achieved, usually within 1 to 2 hours, after single doses of 250 mg and 500 mg, respectively.
Less than 20% of the circulating metronidazole is bound to plasma proteins. Metronidazole is widely distributed into most body tissues and fluids including bone, bile, saliva, pleural and peritoneal fluids, vaginal and seminal fluids, and the CSF after IV administration. Distribution is similar whether the drug is administered orally or by IV infusion. CSF concentrations of metronidazole are approximately 43% of plasma concentrations in patients with inflamed meningitis. The drug also distributes into erythrocytes. It crosses the placenta and enters breast milk. Some accumulation and consequently higher concentrations occur when multiple doses are given. The rate of absorption and peak plasma concentrations of metronidazole is decreased when administered with food; however, the total amount of drug absorbed is not affected.
Adults with normal renal and hepatic functions have been reported to have an average plasma half-life of 6-8 hours. A significant amount of metronidazole (30-60%) is metabolized in the liver by hydroxylation, oxidation and glucuronide conjugation. The major metabolite is 2-hydroxymethyl metronidazole, which has some antibacterial and antiprotozoal activity.
Approximately 20% of metronidazole is excreted in urine and 3% in feces within 24 hours. After 5 days, the amount excreted in the urine increases to 77% and that excreted in feces to 14%. Fecal excretion accounts for 6% to 15% of the given dose. Both unchanged drug and metabolites are excreted in the urine and the feces. The mean elimination half-life of metronidazole is roughly 8 hours. Decreased renal function does not appear to alter the single dose pharmacokinetics of metronidazole although the elimination half-life of the metabolites is prolonged. Geriatric patients may have decreased urinary excretion of metronidazole. The drug is removed by hemodialysis but not by peritoneal dialysis. It can color the urine reddish-brown due to water-soluble pigments formed during metabolism.
Infusion: Intravenous administration of a loading dose of 15 mg/kg followed by 7.5 mg/kg metronidazole every 6 hours in healthy adults produces peak plasma concentrations of 26 µg/mL and troughs of 18 mcg/mL at steady-state.