Blouin R A, Bauer L A, Miller D D, Record K E, Griffen W O
Antimicrob Agents Chemother. 1982 Apr;21(4):575-80. doi: 10.1128/AAC.21.4.575.
In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.
在一项非对照研究中，测定了4名正常受试者（总体重[TBW]为65.9至89.1千克）和6名病态肥胖受试者（TBW为111.4至226.4千克）的万古霉素药代动力学。对病态肥胖受试者在胃旁路手术后3至4小时进行了研究。给出了正常对照组和病态肥胖（TBW为111.4至226.4千克）受试者的平均终末半衰期、分布容积和全身清除率。对病态肥胖受试者在胃旁路手术后3至4小时进行了研究。正常对照组和病态肥胖受试者的平均终末半衰期、分布容积和全身清除率分别为4.8小时、0.39升/千克和1.085毫升/分钟·千克，而病态肥胖受试者分别为3.2小时、0.26升/千克TBW和1.112毫升/分钟·千克TBW。两组之间的平均终末半衰期和分布容积值有显著差异。发现TBW与分布容积（相关系数为0.943）和全身清除率（相关系数为0.981）均有很强的相关性。这些结果表明，应使用TBW来计算病态肥胖患者的万古霉素剂量。这一观点得到以下发现的支持：两组中产生平均稳态浓度为15微克/毫升所需的日剂量（毫克/千克·天）无显著差异（正常体重受试者为23.4±1.5毫克/千克·天，胃旁路手术后病态肥胖受试者为24.0±3.4毫克/千克·天TBW）。因此，为达到相同的平均稳态浓度，病态肥胖患者所需的总剂量（毫克/天）高于正常体重受试者。此外，正常体重和病态肥胖受试者的中央室容积相似（分别为7.7升和6.4升）。为避免肥胖患者给予较大总剂量（毫克/天）时出现高瞬态峰浓度，维持剂量可更频繁地给药。病态肥胖患者观察到的较短平均终末半衰期允许更频繁给药而不会过度蓄积。
