Pharmacokinetics and bioavailability of metronidazole after tablets, suppositories and intravenous administration

The pharmacokinetics of metronidazole were determined in cross-over study on 11 healthy volunteers after 400 mg tablets from two producers. 1000 mg suppositories and 800 mg intravenously (IV). High-pressure liquid chromatography was used to assay both unchanged metronidazole (M) and the hydroxy metronidazole metabolite (OH-M). The peak concentrations were observed 1.2 - 1.3 hrs after the administration of tablets and 4.9 hrs after the suppositories. After the IV dose, the OH-M peak appeared only after 8 hours. The serum half-life was 6.5 hrs after the IV dose, 6.1 - 6.8 hrs after the tablets and 6.8 hrs after the suppositories. After IV dosage, the terminal phase distribution volume was 38.1 lit and the total body clearance 4.09 lit/hr. The bioavailability of the tablets was 80.4 and 84.1 per cent and after the suppositories 53.8 per cent. The rate of elimination OH-M was faster after suppositories than after IV dosage where it was intermediate after the tablets. Accordingly, the serum-half-life was 9.7 hrs after suppositories, 19.2 hrs after IV infusion, and 10.6 and 11.8 hrs. after the tablets. The rates of apparent metabolization was graded in the same relative order, with a faster rate after the suppositories, 0.168 hrs-1 compared to 0.368 hrs-1 after the IV route of administration. The differences pertaining to OH-M is considered probably to be caused by interaction with the metabolic activity of the bacterial flora of the colon.