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

Current fluconazole dosing strategies can be described using either standardized doses (800 or 400mg) or as weight-based dosing recommendations (12 mg/kg loading dose followed by 6 mg/kg maintenance dose). The ideal method of fluconazole dosing is still unclear for certain patient populations, such as those receiving renal replacement therapy or the morbidly obese. We describe a 48-year-old man with a body mass index of 84kg/m(2) who was receiving continuous venovenous hemofiltration (CVVH) and was treated with fluconazole by using a weight-based dose determined by lean body weight, infused at a rate of 200mg/hour. Blood samples were collected at hour 0 (i.e., similar to 24hrs after the loading dose was administered) and at 3.5, 6.8, and 11.3hours after the start of the 600-mg maintenance dose, infused over 3hours. Pharmacokinetic parameters calculated were maximum serum concentration 9.64mg/L, minimum serum concentration 5.98mg/L, area under the serum concentration-time curve from 0-24hours (AUC(0-24)) 184.75mg/L center dot hour, elimination rate constant 0.0199hour(-1), elimination half-life 34.8hours, and total body clearance 3.25L/hour. Our data, when combined with previously published literature, do not support using a linear dose-to-AUC approximation to estimate drug dosing needs in the critically ill patient population receiving CVVH. In addition, our results suggest that morbidly obese patients are able to achieve pharmacodynamic goals defined as an AUC:MIC ratio higher than 25 by using a lean body weight for fluconazole dosing calculations.