Cohen L G, DiBiasio A, Lisco S J, Hurford W E
Department of Pharmacy Practice, Bouve College of Pharmacy and Health Sciences, Northeastern University, Boston, Massachusetts, USA.
Pharmacotherapy. 1997 Sep-Oct;17(5):1023-6.
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.
目前的氟康唑给药建议是基于从正常体重受试者和患者的血清浓度数据计算得出的药代动力学参数。由于肥胖引起的生理变化可能会影响药物的药代动力学，因此将这些建议应用于肥胖个体时可能不准确。一名39岁的病态肥胖男子（BMI 48.3 kg/m²）接受了每日1200 mg氟康唑的治疗，静脉滴注6小时。治疗14天后，在输液后0、1、2、4、8、12、18和24小时采集血样，并使用生物测定法测定稳态血清浓度。计算得出的药代动力学参数为浓度-时间曲线下面积（AUC(0-24)）574.9 mg/L·小时、平均稳态血清浓度23.9 mg/L以及氟康唑清除率139.4 ml/分钟。与已发表的数据相比，我们的患者曲线下面积较低，氟康唑清除率增加。这些变化可能是由于药物分布容积增加所致。基于这些数据以及氟康唑良好的毒性特征，我们建议考虑在此类病态肥胖患者中使用更高的剂量。
