Metronidazole vaginal gel 0.75% (MetroGel-Vaginal): a brief review.

KEY WORDS bacterial vaginosis; metronidazole etronidazole vaginal gel 0.75% (MetroGel-Vaginal(R), 3M Pharmaceuticals, St. Paul, MN) is the intravaginal form of the antibacterial, anti-protozoal agent metronidazole. MetroGel-Vaginal is indicated for the treatment of bacterial vaginosis (BV) and has been shown to be as effective as the oral form of metronidazole for this condition. Recently , a single daily five-day dosing regimen was approved by the Food and Drug Administration. z The prior dosing regimen was twice daily for five days.The current product labeling allows for either dosing regimen to be used. Metronidazole is a nitroimidazole derivative. Its chemical name is 2-methyl-5-nitroimidazole-1-ethanol. Metronidazole vaginal gel 0.75% is administered as a single 5-g dose via intravaginal appli-cator. Each gram of MetroGel-Vaginal contains 7.5 mg of metronidazole in a gelled, purified water solution , containing 0.8 mg of methylparaben, 0.2 mg of propylparaben, propylene glycol, carbomer 934p, sodium hydroxide (to adjust pH), and edetate di-sodium. The gel is formulated at pH 4.0 (normal vaginal pH) and is free of mineral oil. Each appli-catorful delivers 5 g of gel, containing approximately 37.5 mg of metronidazole. Metronidazole is a small uncharged molecule that exerts its biologic activity through reduction of its nitro group. 3 Anaerobic or microaerophilic conditions promote activation of metronidazole. 4 The action of metronidazole is believed to consist of three successive steps: s entry of the drug into target cells, activation by a reduction process, and toxic effects of the reduced product. The reduction of the nitro group of the 5-nitroimidazole results in the formation of toxic derivatives, which kill susceptible bacteria by interacting with DNA. 4,5 The reduction of metronidazole in anaerobic organisms most likely occurs in a one-electron step and is assumed to lead first to the formation of a free radical anion. 4,5 The proposed site of metronidazole reduction is the pyruvate phosphoroclastic reaction in which feredoxin serves as the terminal electron accep-tor. 4,s This process, and thus the level of antimi-crobial activity, is markedly influenced by the oxygen tension of the environment. 4 PHARMACOKINETICS The bioavailability of metronidazole varies according to the route of administration. 6 Intravenous or oral administration of metronidazole results in nearly 100% bioavailability, and the drug diffuses readily to nearly all body tissues. 7 Topical administration (rectal or intravaginal) reduces the bio-availability, resulting in lower serum concentrations of the drug.