Fluconazole serum concentrations and pharmacokinetics in an obese patient

Current fluconazole dosing recommendations are based on pharmacokinetic parameters calculated from serum concentration data in subjects and patients of normal weight. These recommendations may be inaccurate when applied to obese individuals due to the physiologic changes of obesity that may influence drug pharmacokinetics. A 39-year-old morbidly obese man (BMI 48.3 kg/m2) was treated with fluconazole 1200 mg/day infused over 6 hours. After 14 days of therapy, blood samples were obtained at 0, 1, 2, 4, 8, 12, 18, and 24 hours after infusion and steady-state serum concentrations were determined using a bioassay. Pharmacokinetic parameters calculated were area under the concentration-time curve (AUC(0-24)) 574.9 mg/L x hour, average steady-state serum concentration 23.9 mg/L, and fluconazole clearance 139.4 ml/minute. Compared with published data, our patient had a lower area under the curve and increased fluconazole clearance. These changes may be due to the drug's increased volume of distribution. Based on these data and the favorable toxicity profile of fluconazole, we recommend considering higher dosages in such morbidly obese patients.