Pharmacology: Pharmacodynamics: Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L contains miconazole nitrate for antifungal effect and metronidazole for antibacterial and antitrichomonal effects, and also lidocaine for local anesthetic effect.
Miconazole nitrate which is a synthetic imidazole derivative antifungal agent has a wide spectrum of activity and is particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole nitrate is effective against gram-positive bacteria. Miconazole nitrate shows its effect during ergosterol synthesis in the cytoplasmic membrane. Miconazole nitrate changes permeability of the mycotic cell of Candida spp and inhibits glucose utilization in vitro.
Metronidazole, a 5-nitroimidazole derivative, is an antiprotozoal and antibacterial agent effective against several infections caused by anaerobic bacteria and protozoa eg, Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria including anaerobic Streptococci.
Miconazole nitrate and metronidazole have no synergistic or antagonistic effect when administered concomitantly.
Neo-Penotran Forte-L contains lidocaine which stabilizes the neuronal membrane by inhibiting the conduction of impulses, thereby producing local anesthetic action.
Pharmacokinetics: Absorption: Miconazole Nitrate: Absorption of miconazole nitrate through the intravaginal route is very low (approximately 1.4% of the dose). Following intravaginal application of Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L vaginal suppositories daily for 3 days, miconazole nitrate could not be detected in plasma.
Distribution: Metronidazole: Bioavailability of metronidazole by the intravaginal route is 20% compared to the oral administration. Steady-state level of metronidazole in plasma have reached 1.6-7.2 mcg/mL after application of Neo-Penotran and ranged 1.1-5 mcg/mL after application of Neo-Penotran Forte or daily administration of Neo-Penotran Forte-L vaginal suppository once daily for 3 days.
Biotransformation: Metronidazole is metabolized in the liver by oxidation. Major metabolites of metronidazole, hydroxyl and acetic metabolites are excreted in the urine. The hydroxyl metabolite has 30% of biologic activity of metronidazole.
Elimination: The t½ of metronidazole is 6-11 hrs. After oral or IV application of metronidazole, 60-80% of the dose is excreted renally and as metabolites. Approximately 20% of the dose is excreted unchanged in the urine.
Lidocaine: The onset of its action is 3-5 min. Lidocaine is absorbed following topical administration to injured or abraded skin and mucous membranes and metabolized rapidly by the liver. The metabolites and unchanged drug (10% of the dose administered) are excreted by the kidneys. Following intravaginal application of the vaginal suppository daily for 3 days, lidocaine was absorbed minimally and levels in plasma ranged 0.04-1 mcg/mL.