Mechanism of Action
Based on its heterocyclic chemical structure, the drug belongs to the triazoles (containing a five-membered ring with three nitrogen atoms).
The mechanism of action is based on high affinity and selectivity for the fungal enzyme 14$\alpha$-demethylase. A critical pharmacodynamic advantage of fluconazole over imidazole derivatives (e.g., ketoconazole) is its selectivity: the drug practically does not block human 17,20-desmolase. Consequently, it does not disrupt the synthesis of endogenous sex hormones and glucocorticoids.
Pharmacokinetics
Fluconazole is a hydrophilic compound administered both orally and intravenously.
- Absorption: Well absorbed when taken orally, with bioavailability reaching nearly 100%. A critical difference from ketoconazole and itraconazole is that fluconazole absorption does not depend on gastric pH.
- Distribution: The drug distributes readily into all body fluids. It achieves therapeutic concentrations in sputum, urine, saliva, and—most importantly for clinical practice—in cerebrospinal fluid (CSF).
- Elimination: Excreted primarily by the kidneys.
Indications
Fluconazole is used to treat systemic mycoses and dermatophytoses. It is the drug of choice for:
- Systemic candidiasis;
- Cryptococcal meningitis;
- Coccidioidal meningitis.
Note: Using fluconazole for meningitis avoids the intrathecal administration of amphotericin B, which is associated with severe complications.
The drug is also used in etiotropic therapy for dysbiosis. Broad-spectrum antibiotics kill beneficial mucosal microflora, lower local immunity, and trigger the active proliferation of opportunistic Candida fungi. Fluconazole is prescribed to suppress this process.
Spectrum Limitations:
- Completely ineffective against Aspergillus species.
- Less effective than itraconazole in treating blastomycosis, histoplasmosis, and sporotrichosis.
Side Effects and Interactions
The drug has a favorable toxicity profile, which accounts for its widespread clinical use.
- Common reactions (~10%): Gastrointestinal disturbances (nausea, vomiting, abdominal pain, diarrhea).
- Long-term therapy: Reversible alopecia (hair loss) may occur.
- Rare but severe complications: Stevens-Johnson syndrome, hepatic failure.
Drug Interactions: Concurrent administration of barbiturates decreases blood concentrations of fluconazole.
Formulations
The medication is available in the following formulations:
- Capsules (50, 100, 150, and 200 mg);
- Syrup (0.5%);
- Intravenous solution (0.2%).
Oral and intravenous dosages range from 50 mg to 400 mg daily.