Fluconazole Medicine is a Triazole Antifungal used to treat various infections including candidiasis.
Indication
Fluconazole Medicine can be administered in the treatment of the following fungal infections.
- 1) Vaginal yeast infections caused by Candida
- 2) Systemic Candida infections
- 3) Both esophageal and oropharyngeal candidiasis
- 4) Cryptococcal meningitis
- 5) UTI (urinary tract infection) by Candida
- 6) Peritonitis (inflammation of the peritoneum) caused by Candida.
Pharmacodynamics
Fluconazole Medicine has been demonstrated to show fungistatic activity against the majority of strains of the following microorganisms, curing fungal infections.
Candida albicans, Candida glabrata (Many strains are intermediately susceptible), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans
This is achieved through steroidal inhibition in fungal cells, interfering with cell wall synthesis and growth as well as cell adhesion, there by treating fungal infections and their symptoms.
The fungistatic activity of Fluconazole Medicine has also been shown in normal and immunocompromised animal models with both systemic and intracranial fungal infections caused by Cryptococcus neoformans and for systemic infections caused by Candida albicans. It is important to note that resistant organisms have been found against various strains of organisms treated with Fluconazole Medicine. This further substantiates the need to perform susceptibility testing when Fluconazole Medicine is considered as an antifungal therapy.
Mechanism of action
Fluconazole Medicine is a very selective inhibitor of fungal cytochrome P450 dependent enzyme lanosterol 14-α-demethylase. This enzyme normally works to convert lanosterol to ergosterol, which is necessary for fungal cell wall synthesis. The free nitrogen atom located on the azole ring of Fluconazole Medicine binds with a single iron atom located in the heme group of lanosterol 14-α-demethylase. This prevents oxygen activation and, as a result, inhibits the demethylation of lanosterol, halting the process of ergosterol biosynthesis. Methylated sterols are then found to accumulate in the fungal cellular membrane, leading to an arrest of fungal growth. These accumulated sterols negatively affect the structure and function of the fungal cell plasma membrane.
Fluconazole Medicine resistance may arise from an alteration in the amount or function of the target enzyme (lanosterol 14-α-demethylase), altered access to this enzyme, or a combination of the above.8 Other mechanisms may also be implicated, and studies are ongoing.
Absorption
The pharmacokinetic properties of Fluconazole Medicine are comparable after administration by the intravenous (IV) and oral (PO) routes. In healthy volunteers, the bioavailability of orally administered fluconazole is measured to be above 90%. It is extensively absorbed in the gastrointestinal tract when an oral dose is taken. Oral absorption is not affected by food intake with fluconazole but may increase the time until the maximum concentration is reached.
Tmax (or the time taken to achieve the maximum concentration) in one clinical study of healthy patients receiving 50 mg/kg of Fluconazole Medicine was 3 hours.
Peak plasma concentrations (Cmax) in fasting and healthy volunteers occur between 1-2 hours post-dose. Steady-state concentrations are achieved within 5 to 10 days after oral doses of 50-400 mg administered once daily. Administration of a loading dose on the first day of fluconazole treatment, or twice the usual daily dose, leads to plasma concentrations close to steady-state by the second day. The mean AUC (area under the curve) was 20.3 in healthy volunteers receiving 25 mg of fluconazole.
Protein binding
The protein binding of Fluconazole Medicine is low and is estimated to be 11 to 12%.
Volume of distribution
The apparent volume of distribution is said to be similar to the volume of distribution of total body water.
Metabolism
Fluconazole Medicine is metabolized minimally in the liver. Fluconazole is an inhibitor of CYP2C9, CYP3A4 and CYP2C19. Two metabolites were detected in the urine of healthy volunteers taking a 50 mg radiolabeled dose of fluconazole; a glacier-onidated metabolite on the hydroxyl moiety (6.5%) and a fluconazole N-oxide metabolite (2%). The same study indicated that no signs of metabolic cleavage of fluconazole were observed, suggesting a difference in metabolism when compared to other agents in the same drug class, which are heavily metabolized in the liver.
Fluconazole Medicine Route of Elimination
In normal volunteers, Fluconazole Medicine is cleared primarily by renal excretion, with approximately 80% of the administered dose measured in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites.
Half-life
The terminal elimination half-life in the plasma is approximately 30 hours (range: 20-50 hours) after oral administration.
Clearance
This drug is mainly eliminated by the kidneys and the mean body clearance in adults is reported to be 0.23 mL/min/kg.
Toxicity
Acute oral toxicity (LD50): 1271 mg/kg (rat)
Fluconazole Medicine Overdose information
Fluconazole Medicine overdoses have been associated with hallucination and paranoia, sometimes in combination. In cases of overdose, employ supportive treatment. Gastric lavage may be necessary. Other modalities such as forced diuresis or hemodialysis may also be used.
Food Interactions
Take with or without food. The absorption is unaffected by food.