Systemic concentrations of metronidazole and its main metabolites after intravenous oral and vaginal administration

Metronidazole kinetics was studied in 5 healthy women after a single dose given intravenously, orally or vaginally, 500, 400 and 500 mg, respectively. Serum levels of the drug and of its hydroxy and acid metabolites were assessed. The results after intravenous and oral boluses were consistent with previous reports. After vaginal dose maximum serum levels of about 1 microgram/ml of the drug were obtained between 9 and 24 h after the dose. Maximum concentration of the hydroxy metabolite was about 0.3 microgram/ml after 24 h. Bioavailability of the drug was 19 +/- 3% after the vaginal dose as compared to 100 +/- 5% after the oral dose. Daily insertion into the vagina of 500 mg metronidazole resulted in a maximum serum concentration of 1.2 +/- 0.2 microgram/ml of the parent drug and of 0.6 +/- 0.1 microgram/ml of the hydroxy metabolite after about 3 days (range 2-4) after which no accumulation was noted. Urinary excretion of the metabolites was considerably lower after vaginal than after intravenous or oral administration, but the proportion between the two metabolites in the urine was constant.