Gynomax Mechanism of Action

Pharmacology: Pharmacodynamics: Tioconazole is a synthetic antifungal agent with a high in-vitro efficacy to yeast and fungi (including dermatophytes).
Also, it is effective against Trichomonas vaginalis, Gardnerella vaginalis, Bacteroides spp., and some Gram (+) bacteria (including Staphylococcus and Streptococcus spp.). In clinical studies, tioconazole is found to be effective in the treatment of Candida albicans and other Candida species (Torulopsis glabrata) and to vaginal infections caused by Trichomonas vaginalis.
Tioconazole shows its effect by altering permeability of the fungal cell membrane. Ergosterol is an essential component of the fungal cell membrane. Tioconazole inhibits the ergosterol synthesis by interacting with 14α-demethylase, a cytochrome P450 enzyme that converts lanosterol to ergosterol. Inhibition of ergosterol synthesis leads to increase of cellular permeability and therefore to leakage of intracellular phosphorus compounds and potassium across the cell membrane.
Tinidazole is effective against protozoans and anaerobic bacteria. Its antiprotozoal activity includes Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia. Tinidazole is effective against Gardnerella vaginalis and to the majority of anaerobic bacteria (Bacteroides fragilis, Bacteroides melaninogenicus, Bacteroides spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella spp.).
The complete mechanism of action of tinidazole has not been fully clarified. The reduction of the nitro group is mediated by a ferrodoxin system and a low oxidation reduction potential which is only generated by anaerobic bacteria. This may be the reason for anaerobes having a higher tinidazole uptake than aerobes, although tinidazole can penetrate cell membranes of both types of microorganisms. The reduction process creates reactive intermediates and a diffusion gradient, which enhances tinidazole uptake.
Lidocaine is an amide-type local (topical) anesthetic. It stabilizes the neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby producing local anesthetic action.
Pharmacokinetics: Absorption: Tinidazole: Approximately 10% of tinidazole is absorbed after intravaginal application. Mean peak plasma level was found to be 1.0 μg/mL, and the time to reach this level (tmax) was found as 8.7 hours following administration of vaginal suppository containing 500 mg tinidazole to 6 healthy volunteers.
Tioconazole: Tioconazole has a negligible systemic absorption after intravaginal application. Mean peak plasma concentration following the administration of 300 mg single dose tioconazole ointment to women with candidal vulvovaginitis was found as 18 ng/mL.
Lidocaine: Lidocaine is absorbed in very low quantities from abraded skin and mucous membranes.
Distribution: Tinidazole: Tinidazole is almost distributed into all tissues and body fluids and crosses the blood-brain barrier. The volume of distribution is 50 liters. Plasma protein binding of tinidazole is 12%. Tinidazole crosses the placental barrier and is secreted in breast milk.
Tioconazole: In most clinical studies, after a single dose (300 mg) intravaginal tioconazole administration, concentrations in vaginal fluid are found to inhibit Candida albicans reproduction for 2-3 days. It is not known whether tioconazole is secreted in breast milk.
Lidocaine: Plasma protein binding is 60% - 80%. It crosses the placenta and blood-brain barrier by passive diffusion and is distributed to cerebrospinal fluid, tissues with high perfusion (kidney, liver, heart) and fatty tissue. Distribution volume is 0.8-1.3 L/kg.
Biotransformation: Tinidazole: Tinidazole is partly metabolized by oxidation, hydroxylation, and conjugation. Tinidazole is biotransformed mainly by CYP3A4.
Tioconazole: Primary metabolite of tioconazole is glucuronide conjugate.
Tioconazole does not appear to be metabolized in vaginal fluid, but a portion of the drug that is absorbed systemically following intravaginal application is metabolized. One reported metabolite is formed from N-glucuronidation of a nitrogen on the imidazole ring, another is formed by O-dethienylation of a chlorothienyl group, hydration to an alcohol, and glucuronidation.
Lidocaine: It is metabolized in the liver. The active metabolites are monoethylglycinexylidide (MEGX) and glycinexylidide (GX).
Elimination: Tinidazole: The plasma half-life of tinidazole is approximately 12-14 hours. Tinidazole is excreted by the liver and the kidneys.
Tinidazole is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose).
Approximately 12% of the drug is excreted in the feces.
Tioconazole: After intravaginal application of tioconazole, drug is usually eliminated from plasma in 72 hours.
Following oral tioconazole administration, 25-27% of the dose is excreted in urine as metabolites and 59% of the dose is excreted in feces (principally as unchanged drug).
Lidocaine: After intravenous administration, 90% of the drug is excreted as metabolites and less than 10% is excreted as unchanged drug in urine.
Toxicology: Preclinical safety data: The active ingredients of Tioconazole + Tinidazole + Lidocaine (Gynomax), are well known, regularly used substances, and are described in pharmacopoeias. New preclinical safety studies are not conducted because many toxicological studies are available for these substances.