Metromic/Metromic Forte Mechanism of Action

Pharmacotherapeutic group: Gynecological anti infectives and antiseptics, imidazole derivatives. ATC code: G01AF20.
Pharmacology: Pharmacodynamics: Metronidazole + Miconazole (Metromic) 500 mg/100 mg and Metronidazole + Miconazole (Metromic Forte) 750 mg/200 mg Vaginal Suppositories contain miconazole nitrate for antifungal and metronidazole for antibacterial and antitrichomonal effects. Miconazole nitrate which is a synthetic imidazole derivative antifungal has a wide spectrum of activity and is particularly effective against pathogen fungi including Candida albicans. In addition, miconazole nitrate is effective against gram (+) bacteria. Miconazole nitrate shows its effect by ergosterol synthesis in the cytoplasmic membrane. Miconazole nitrate changes permeability of the mycotic cell of candida species and inhibits glucose utilization in vitro.
Metronidazole, a 5-nitroimidazole derivative is an antiprotozoal and an antibacterial agent and is effective against several infections caused by anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria including anaerobic streptococci.
Miconazole nitrate and metronidazole have no synergic or antagonistic effects.
Pharmacokinetics: Absorption: Miconazole nitrate: Absorption of miconazole nitrate by the intravaginal route is very low (approximately 1.4% of dose). Following intravaginal application of Metronidazole + Miconazole (Metromic) 500 mg/100 mg and Metronidazole + Miconazole (Metromic Forte) 750 mg/200 mg Vaginal Suppositories, miconazole nitrate could not detected in plasma.
Metronidazole: Bioavailability of metronidazole by vaginal route is 20% compared to the oral route. Steady state levels of metronidazole in plasma ranged 1.6-7.2 µg/mL after daily intravaginal application of Metronidazole + Miconazole (Metromic) 500 mg/100 mg and Metronidazole + Miconazole (Metromic Forte) 750 mg/200 mg Vaginal Suppositories.
Distribution: Miconazole nitrate: The protein binding rate is 90%-93%. Its distribution to cerebrospinal fluid is poor; however it is widely distributed to other tissues. Distribution volume is 1400 L.
Metronidazole: It is widely distributed in body tissues and fluids including bile, bone, breast, milk, cerebral abscesses, cerebrospinal fluid, liver and liver abscesses, saliva, seminal fluids and vaginal secretion and achieves concentrations similar to those in plasma. It crosses the placenta and rapidly enters to fetal circulation. Not more than 20% is bound to plasma proteins. Distribution volume is 0.25-0.85 L/kg.
Metabolism: Miconazole nitrate: It is metabolized in liver. Two non-active metabolites found are 2,4-dichlorophenyl-1 H imidazole ethanol and 2,4-dichloromandelic acid.
Metronidazole: It is metabolized in the liver by oxidation, hydroxy metabolite is active. Major metabolites of metronidazole, hydroxy and acetic acid metabolites, are excreted in urine. The hydroxyl metabolite has 30% of biological activity of metronidazole.
Elimination: Miconazole nitrate: Half-life is 24 hours. Less than 1% is excreted in the urine.
Metronidazole: Half-life is 6-11 hours. About 6%-15% of metronidazole dose is excreted with faeces, 60%-80% is unchanged and excreted in urine as its metabolites. Approximately 20% of metronidazole is excreted in the urine as unchanged drug.