Pharmacokinetics and the most suitable dosing regimen of fluconazole in critically ill patients receiving continuous hemodiafiltration.

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.