Comparison of the pharmacokinetics of metronidazole in healthy female volunteers following either a single oral or intravenous dose

1 The plasma pharmacokinetics of metronidazole following a single dose (500 mg) of metronidazole have been investigated in a crossover study in healthy female volunteers, using assays specific for metronidazole and its metabolites 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole (metabolite I) and 2-methyl-5-nitroimidazole-1-acetic acid (metabolite II).

2 No systematic differences, which could be related to the route of metronidazole administration, were observed in the area under the plasma metronidazole concentration against time curve, elimination half-life, apparent volume of distribution, or total urinary excretion of metronidazole. Following a single oral or intravenous dose, the half-life estimates were 7.0 h and 7.3 h respectively.

3 No metabolite II was detected in plasma following the administration of metronidazole by either route. Urinary elimination of this metabolite appeared to be independent of the route of administration.

4 No systematic differences, which could be related to the route of administration, were observed in the apparent half-life or total urinary excretion of metabolite I. However, the area under the plasma concentration against time curve for metabolite I was significantly greater (+27%) following oral administration than following intravenous administration.

5 A single dose of metronidazole (500 mg) produced a peak plasma concentration for the drug which was in excess of the minimum inhibitory concentration of most susceptible anaerobic bacteria, and in several of the volunteers such an inhibitory concentration of metronidazole was maintained in plasma for more than 8 h following a single dose.