Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient

Abstract

Fluconazole is effective for the treatment of fungal infections. A continuous venovenous hemofiltration (CVVH) was necessary in a liver transplant patient with anuria. Fluconazole treatment was started after the diagnosis of systemic candidiasis. There was no adverse effect on liver function, and the immunosuppression with cyclosporine was not affected. It is shown for the first time that CVVH effectively removes fluconazole from the blood circulation by a clearance into the hemofiltrate of approximately 21 ml/min. These data suggest that the treatment of fungal infections with fluconazole does not necessitate a reduction of the dosage during CVVH.

Fluconazole Pharmacokinetics in a Morbidly Obese, Critically Ill Patient Receiving Continuous Venovenous Hemofiltration

“…Four studies specifically evaluating fluconazole in patients receiving CVVH were evaluated in comparison with our pharmacokinetic findings (Table ); studies that evaluated hemodiafiltration were excluded. Our patient was found to have a Cl Total of 3.25 L/hour, which exceeds rates of clearance documented in previous CVVH studies . This difference in clearance, when compared with previously published reports, may be accounted for based on variations in membrane filter surface area and a higher rate of hemofiltration.…”

“…Fluconazole undergoes both glomerular filtration and tubular reabsorption, with a total of 80% excreted as unchanged drug and 11% as inactive metabolites in patients with normal renal function. Various methods of renal replacement therapy have shown highly effective elimination of fluconazole with calculated sieving coefficients ranging from 0.76 to 1.02 . Four studies specifically evaluating fluconazole in patients receiving CVVH were evaluated in comparison with our pharmacokinetic findings (Table ); studies that evaluated hemodiafiltration were excluded.…”

“…Previously published studies have shown a linear relationship between fluconazole dose and 24‐hour AUC; however, these data were largely obtained from studies conducted in patients with normal body habitus and normal renal function . More recent data have identified that this correlation may not be reliable in patients who are critically ill, obese, or receiving CVVH (Table ) . For example, in one study fluconazole 1200 mg (6.5 mg/kg total body weight [TBW]) was administered to a morbidly obese 185‐kg patient with necrotizing fasciitis, which only resulted in an AUC 0–24 of 574.9 mg/L•hour .…”

“…9,10 More recent data have identified that this correlation may not be reliable in patients who are critically ill, obese, or receiving CVVH ( Table 1). [11][12][13][14] For example, in one study fluconazole 1200 mg (6.5 mg/kg total body weight [TBW]) was administered to a morbidly obese 185-kg patient with necrotizing fasciitis, which only resulted in an AUC 0-24 of 574.9 mg/ L•hour. 15 Further, another review concluded that currently available data do not support the idea of a consistent dose-to-MIC relationship.…”

Using pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review

“…As shown in Table 2, FLC PK has been described in continuous venovenous haemofiltration (CVVHF) and continuous venovenous haemodiafiltration (CVVHDF) [28][29][30][31][32][33][34]. However, the PK of FLC in critically ill patients undergoing extended daily diafiltration (EDDf) has yet to be described.…”