the serum concentration of Erythromycin (Risk X: avoid combination). Pharmacology Pharmacodynamics Like other imidazole- and triazole-class antifungals, fluconazole inhibits the fungal cytochrome P450 enzyme 14α-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α-methyl sterols. Fluconazole is primarily fungistatic; however, it may be fungicidal against certain organisms in a dose-dependent manner, specifically Cryptococcus. Pharmacokinetics Following oral dosing, fluconazole is almost completely absorbed within two hours. Bioavailability is not significantly affected by the absence of stomach acid. Concentrations measured in the urine, tears, and skin are approximately 10 times the plasma concentration, whereas saliva, sputum, and vaginal fluid concentrations are approximately equal to the plasma concentration, following a standard dose range of between 100 mg and 400 mg per day. The elimination half-life of fluconazole follows zero order, and only 10% of elimination is due to metabolism, the remainder being excreted in urine and sweat. Patients with impaired renal function will be at risk of overdose. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. History Fluconazole was patented by Pfizer in 1981 in the United Kingdom and came into commercial use in 1988. Patent expirations occurred in 2004 and 2005. References External links Doi : Evolution of Fluconazole-Resistant Candida albicans Strains by Drug-Induced Mating Competence and Parasexual Recombination Antiprotozoal agents CYP3A4 inhibitors Fluoroarenes Lanosterol 14α-demethylase inhibitors Pfizer brands Phenylethanolamines Tertiary alcohols Triazole antifungals World Health Organization essential medicines Wikipedia medicine articles ready to translate General cytochrome P450 inhibitors