Objective
To evaluate fluconazole pharmacokinetics and the dosage best suited to maintain effective plasma concentration in patients with continuous hemodiafiltration.Design and setting
Prospective study in the general intensive care unit of a university hospital.Patients
Four critically ill patients being treated with fluconazole and receiving continuous hemodiafiltration.Interventions
Fluconazole was administered at three dosing regimens: 200 and 400 mg every 24 h, 400 mg every 12 h, and 800 mg every 24 h.Measurements and results
The following pharmacokinetic variables for fluconazole were obtained: The mean volume distribution of steady state dosed at 400 mg every 12 h and 800 mg every 24 h were 0.55±0.23 and 0.71±0.16 l/kg, half-life of the elimination phase 8.08±0.83 and 9.12±0.75 h, total body clearance of fluconazole 1.14±0.44 and 0.98±0.20 ml/kg per minute, respectively. None of the dosing regimens reached the effective plasma trough concentration of fluconazole; however, simulation study found the recommended dose.Conclusions
Continuous hemodiafiltration is highly effective in removing fluconazole from circulation. We recommend fluconazole to be dosed at 500–600 mg intravenously every 12 h in patients receiving hemodiafiltration. This dosing regimen resulted in adequate trough plasma levels for systemic fungal infection.Keywords Fluconazole - Pharmacokinetic - Antifungal - Continuous hemodiafiltration - Critically ill patient - Immunocompromised host