Scalpex Mechanism of Action

Pharmacology: Mechanism of Action: Ketoconazole, one of the active ingredients of Ketoconazole + Zinc Pyrithione (Scalpex) Shampoo is a broad spectrum antifungal agent. It acts by altering the permeability of yeast and fungal cell membranes. Inhibition of ergosterol biosynthesis, the major sterol of these cell membranes, is accompanied by accumulation of 14-α-methylsterol. Cholesterol is the main sterol component of cell membranes in mammalian cells, whereas ergosterol is the primary component of those in fungal cells. Since the 14-α-demethylation step in ergosterol biosynthesis is cytochrome P450 dependent, it has been suggested that Ketoconazole may affect biosynthesis by inhibiting cytochrome P450 dependent 14-α-demethylase activity.
This leads to accumulation of 14-α-methylsterols. Accumulation of 14-α-methylsterols, together with the decrease in ergosterol content of the cell membrane, create an unstable condition which leads to disturbed membrane function, compromised cell growth and viability.
At higher concentrations, Ketoconazole caused an accumulation of saturated fatty acids after incubation with Candida albicans, an effect that is expected to further destabilize the structure and permeability of the fungal cell membrane.
Thus, Ketoconazole has a dual action; a fungistatic mechanism at low concentrations which seems to be characteristic of all imidazoles and is related to inhibition of ergosterol biosynthesis and a fungicidal effect at higher concentrations, which is directly produced by damage to the cell membrane.
An MIC of 0.02 mcg/mL is sufficient to inhibit the growth of Pityrosporum yeast. Ketoconazole also has the action on 5-lipooxygenase, thus inhibits leukotriene B4 synthesis and thus inflammation.
Zinc Pyrithione, the other active component of Ketoconazole + Zinc Pyrithione (Scalpex) Shampoo reduces flaking and itching caused by dandruff (keratolytic).
Zinc Pyrithione inhibits membrane transport via a direct or indirect effect on the primary proton pump which energizes transport and that the site of action of pyrithione is likely to be intracellular rather than extracellular.
Zinc Pyrithione causes the leakage of intracellular material.
Zinc Pyrithione is effective at an MIC of 0.12-8 mcg/mL.
Pharmacokinetics: Percutaneous absorption of Ketoconazole and Zinc Pyrithione Shampoo is negligible since blood levels cannot be detected even after chronic shampooing, systemic effects therefore are not expected.