Flucon Mechanism of Action

Pharmacology: Pharmacodynamics and Pharmacokinetics: Fluconazole, a member of the triazole class of antifungal agents, is a potent and selective inhibitor of fungal enzymes necessary for the synthesis of ergosterol.
Fluconazole shows little pharmacological activity in a wide range of animal studies. Some prolongation of pentobarbitone sleeping times in mice (p.o.), increased mean arterial and left ventricular blood pressure and increased heart rate in anaesthetised cats (i.v.) occurred. Inhibition of rat ovarian aromatase was observed at high concentrations.
Fluconazole is highly specific for fungal cytochrome P-450 dependent enzymes.
Fluconazole 50 mg daily, when given for up to 28 days, has been shown not to affect testosterone plasma concentrations in males or steroid concentrations in females of child-bearing age. Fluconazole 200-400 mg daily has no clinically significant effect on endogenous steroid levels or on ACTH stimulated response in healthy male volunteers. Interaction studies with antipyrine indicate that single or multiple doses of fluconazole 50 mg, do not affect its metabolism.
There have been reports of cases of superinfection with Candida species other than C. albicans, which are often inherently not susceptible to fluconazole (e.g. Candida krusei). Such cases may require alternative antifungal therapy.
Fluconazole's pharmacokinetic properties are similar following its oral or intravenous administration. Orally administered fluconazole is well absorbed, with plasma levels (and systemic bioavailability) being over 90% of the levels achieved following intravenous administration. Absorption by the oral route is not affected by the joint administration of food. Maximum plasma concentrations when fasting are obtained between 0.5 and 1.5 hours post-dose, with a clearance half-life of approximately 30 hours.
Plasma concentrations are proportional to the dose. 90% steady state levels are reached after 4 or 5 days with multiple once daily doses. The administration of a higher dose on the first day, double that of the normal daily dose, raises plasma levels to 90% of the equilibrium status levels by the second day.
The apparent volume of distribution is close to that of total body water. Fluconazole achieves good penetration in all body fluids studied. The levels of fluconazole in saliva and sputum are similar to plasma levels. In patients with fungal meningitis, fluconazole levels in the CSF are approximately 80% of the corresponding plasma levels. High skin concentrations of fluconazole, above serum concentrations, are achieved in the stratum corneum, epidermis-dermis and eccrine sweat. Fluconazole accumulates in the stratum corneum. Binding to plasma proteins is low (11-12%).
Clearance is mostly renal, with approximately 80% of the unmodified dose appearing in the urine. The clearance of fluconazole is proportional to creatinine clearance. There is no evidence of circulating metabolites.
Fluconazole's long plasma elimination half-life, makes it possible to administer a single dose in the treatment of genital candidiasis and a daily dose in the treatment of other indications.