title: Fluconazole pharmacokinetics in a morbidly obese, critically ill patient receiving continuous venovenous hemofiltration.
abstract: Current fluconazole dosing strategies can be described using either standardized doses (800 or 400 mg) 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 84 kg/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 200 mg/hour. Blood samples were collected at hour 0 (i.e., ~24 hrs after the loading dose was administered) and at 3.5, 6.8, and 11.3 hours after the start of the 600-mg maintenance dose, infused over 3 hours. Pharmacokinetic parameters calculated were maximum serum concentration 9.64 mg/L, minimum serum concentration 5.98 mg/L, area under the serum concentration-time curve from 0-24 hours (AUC0-24 ) 184.75 mg/L•hour, elimination rate constant 0.0199 hour(-1) , elimination half-life 34.8 hours, and total body clearance 3.25 L/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.
authors: Department of Pharmacy, Massachusetts General Hospital, Boston, Massachusetts.
authors: Natasha D
authors: ND
authors: Lopez
authors: Kristy M
authors: KM
authors: Phillips
mesh_terms: D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016638:Critical Illness; D016903:Drug Monitoring; D015725:Fluconazole / Q000493:pharmacokinetics*; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole
keywords: CVVH; critical care; drug monitoring; fluconazole; hemofiltration; lean body weight; obesity; pharmacokinetics