Canditral Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: CANDITRAL acts by inhibition of Cytochrome-P450 dependent fungal enzyme systems which synthesize ergosterol, the primary cellular sterol in fungi. This leads to disruption of intracellular membranes with inhibition of lanosterol demthylase leading to accumulation of membrane precursor lipids such as lanosterol.
CANDITRAL has less affinity for mammalian cytochromes as compared to Ketoconazole and thus causes a lower incidence of adverse effects than Ketoconazole.
Pharmacokinetics: Absorption of CANDITRAL after oral administration is maximal immediately after a main meal. Peak plasma concentrations are achieved after 14 days of administration and the concentrations attained with 100 mg daily are effective against most common fungal pathogens.
CANDITRAL is highly keratophilic and lipophilic and is widely distributed in the body, achieving concentrations in fatty tissues, omentum, liver, kidney, nails and skin tissues that are 2-20 times higher than corresponding plasma concentrations. Fluids equivalent to body water such as CSF, eye fluid and saliva contain low to negligible amounts of CANDITRAL whereas exudates like pus have up to 3.5 times the simultaneous plasma concentration. Most tissues which are prone to fungal invasion such as skin and female genital tract issues have several times the plasma concentration of CANDITRAL.
The major route of CANDITRAL delivery to the skin appears to be via sebum. Sebum levels of CANDITRAL are 5 to 10 times higher than corresponding plasma levels within 4 days of starting the drug and detectable amounts persist for up to 14 days after the drug is stopped. CANDITRAL can be detected in stratum corneum up to 4 weeks after discontinuing therapy, which reflects the drug's affinity for sebum and keratinocytes. CANDITRAL is 99.8% bound, 94.9% to plasma proteins (primarily albumin) and 4.9% to blood cells leaving only 0.2% as free drug.
CANDITRAL undergoes extensive hepatic metabolism prior to being excreted in inactive form in urine and bile. The major metabolite of CANDITRAL is Hydroxyitraconazole. Elimination half life is about 20 hours after a single oral dose of 100 mg and approximately 30 hours following 2 to 4 weeks treatment with CANDITRAL 100 mg once daily.