Pharmacokinetics of intravaginal metronidazole gel

The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48-hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500-mg oral dose. The dose-adjusted maximum serum concentration (898 +/- 121 ng/mL vs. 237 +/- 69 ng/mL) and area under the serum concentration-time curve (9362 +/- 2873 ng * hr/mL vs. 4977 +/- 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 +/- 0.6 hr vs. 8.4 +/- 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacterial vaginosis.