Fluconazole: optimized antifungal therapy based on pharmacokinetics.

Area of Science:

• Pharmacology
• Mycology

Background:

• Fluconazole is a triazole antifungal agent.
• It inhibits ergosterol synthesis by targeting C-14-Demethylase, an enzyme dependent on Cytochrom-P-450.
• Drug interactions affecting Cytochrom-P-450 necessitate careful dosing considerations for fluconazole.

Purpose of the Study:

• To review the pharmacokinetics and pharmacodynamics of fluconazole.
• To discuss susceptibility testing and the potential for dose escalation.
• To evaluate high-dose fluconazole therapy in specific patient populations.

Main Methods:

• Review of existing literature and clinical data.
• Analysis of pharmacokinetic properties including bioavailability and tissue penetration.
• Examination of susceptibility testing standards (M27 method) and minimal inhibitory concentrations (MICs).

Main Results:

• Fluconazole exhibits high oral bioavailability (>90%) and excellent penetration into body fluids and tissues.
• A linear dose-concentration relationship allows for potential dose escalation for less susceptible fungi.
• Limited prospective data support high-dose fluconazole efficacy and tolerability in surgical and intensive care settings.

Conclusions:

• Fluconazole dosing requires consideration of drug interactions and patient-specific factors.
• High-dose therapy may be viable for certain fungal infections, supported by consensus recommendations.
• Dosage adjustments are necessary for patients undergoing haemofiltration or haemodialysis.