Pharmacokinetics of intravenous metronidazole at different dosages in healthy subjects.

Metronidazole is effective in the treatment of trichomoniasis and serious anaerobic infections. Individual doses given clinically ranged from 250 mg to 2.0 gm. Most of the available pharmacokinetic data were obtained when the drug was administered at the low end of the dosage range. Several other studies were done using assays that were subject to interference by metabolites. We therefore conducted this investigation to evaluate the pharmacokinetics of metronidazole at different dosage levels in normal subjects in a crossover manner using a specific HPLC assay. Nine male normal volunteers were each administered 250 mg, 1.0 gm and 2.0 gm of intravenous metronidazole in a crossover manner. Serial blood samples were obtained immediately before and at 0, 15, 30, 60, 90 minutes, 2, 4, 6, 10, 24 and 32 hours after the dose. Serum concentrations of metronidazole and its metabolites were determined by HPLC. The half-lives, elimination rate constants, volumes of distribution and areas under the concentration-time curve were calculated. Analysis of variance revealed a statistically significant difference between the low dose (250 mg) and the high dose (1.0 gm and 2.0 gm) effect on the calculated pharmacokinetic parameters. In addition, the production and the elimination of the metronidazole hydroxy metabolite were also found to be reduced when higher doses of the drug were administered. These findings revealed that the pharmacokinetics of metronidazole and its hydroxy metabolite are altered when higher doses of the drug are given; the metabolic transformation of the parent drug is also expected to be reduced.