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.


METHODS
Prospective study in the general intensive care unit of a university hospital.


METHODS
Four critically ill patients being treated with fluconazole and receiving continuous hemodiafiltration.


METHODS
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.


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.
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000935:Antifungal Agents; D015725:Fluconazole