Tri-V Mechanism of Action

Pharmacology: Pharmacodynamics: TRI-V contains miconazole nitrate for antifungal, metronidazole for antibacterial and antitrichomonal effects and lidocaine for local anaesthetic effect.
Miconazole nitrate which is a synthetic imidazole antifungal agent has a wide spectrum of activity and is particularly effective against pathogen fungi including Candida albicans and is effective against Gram positive bacteria. 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. Lidocaine stabilizes the neuronal membrane by inhibiting the conduction of impulses, thereby producing local anesthetic action.
Pharmacokinetics: Absorption: Miconazole nitrate absorption by the intravaginal route is very low (approximately 1.4% of dose). Bioavailability of metronidazole by the intravaginal route is approximately 20% compared to oral administration. Lidocaine is absorbed from injured skin and mucous membranes in very low amounts.
Distribution: Miconazole nitrate has a problem binding ratio about 90-93%. It shows weak distribution to cerebrospinal fluid while it distributes widely to other tissues. Volume of distribution is 1,400 L. Metronidazole distributes to body tissues and fluids like gall bladder, bone, breast milk, cerebral abscess, saliva, seminal and vaginal fluids widely and in nearly same concentrations as plasma. Plasma protein binding ratio is not more than 20%. Distribution volume is 0.25-0.85 L/kg. Lidocaine applied through oral or intravenous route is determined in bowels, urine and in low amounts in faeces. It is found in the urine as unchanged drug and its metabolites. Lidocaine binds with plasma proteins (primarily to α1-acidglycoprotein, less to albumin) in a ratio 33%-80%. Distribution volume is 0.8-1.3 L/kg.
Biotransformation: Miconazole nitrate is metabolized in liver. Has two metabolites that are inactive. (2, 4-dichlorophenyl-1 H imidazole ethanole and 2, 4-dichloromandelic acid). Metronidazole is metabolized in the liver by oxidation. Its hydroxy metabolite is active. Major metabolites of metronidazole, hydroxy and acetic acid metabolites, are excreted in urine. The hydroxy metabolite has a 30% of biologic activity of metronidazole. Lidocaine is metabolized in the liver. Has active metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX).
Elimination: Miconazole nitrate has half-life of 24 hours. Less than 1% of it is excreted by kidneys. 50% of it is excreted unchanged with faeces. By systemic or topical application 6-15% of metronidazole dose is excreted by faecal route, 60-80% unchanged and as metabolites in the urine. The ratio of the drug excreted unchanged in the urine is 20%. Lidocaine is excreted in urine as metabolites and unchanged form (10% of the applied dose).