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.