Albany Medical Center, Albany, New York.
Pharmacotherapy. 2013 Dec;33(12):1278-87. doi: 10.1002/phar.1345. Epub 2013 Sep 9.
To compare the likelihood of alternative vancomycin dosing strategies based on weight, height, or body surface area (BSA) in achieving isometric vancomycin area under the serum concentration-time curve (AUC) values across the body size distribution of children and young adults.
Maximum a posteriori probability Bayesian (MAP-Bayesian) pharmacokinetic analysis using retrospectively collected medical record data.
Children's hospital.
A total of 115 patients 1-20 years of age managed outside of the intensive care unit who were treated with vancomycin between May 1, 2011, and August 31, 2012, and had a minimum of two serum vancomycin concentration measurements.
Vancomycin dosing and concentration-time information along with demographic and laboratory data related to kidney function estimation were extracted from the patients' medical records. A previously structured one-compartment model was used to derive MAP-Bayesian estimates of pharmacokinetic system parameters for each patient. Post hoc linear and power function regression were used to compare clearance (Cl) and the volume of distribution of the central compartment (Vc) to body size descriptors (weight, height, and BSA). The relationship of the body size descriptor-indexed parameter across the body size distribution was assessed. The AUC from time 0 to 24 hours (AUC24 ) values associated with vancomycin dosing regimens based on weight, height, and BSA were estimated. The 115 patients (56.5% male) had a mean ± SD age, height, and weight of 9.7 ± 5.4 years, 133 ± 32.3 cm, and 38.0 ± 24.2 kg, respectively. Each patient received a minimum of four doses of vancomycin and had two to nine serum vancomycin concentration measurements, for a total of 313 measurements for all patients. Vancomycin Cl was a nonlinear function of weight and a linear-proportionate function of BSA, whereas the volume of distribution of the central compartment (Vc) was a linear-proportionate function of weight. The expected median (5th-95th percentile) AUC24 values with weight-based dosing of vancomycin 60-70 mg/kg/day were 446 (315-834) mg·hour/L and 649 (385-1165) mg·hour/L in patients weighing less than 40 kg (n=72) and those weighing 40 kg or more (n=43), respectively. In contrast, isometric AUC24 values were predicted with BSA-based dosing across the body size distribution.
BSA-based dosing is more likely than weight-based (mg/kg) dosing of vancomycin to achieve isometric AUC24 values across the body size distribution of children and young adults. Pharmacokinetic studies that compare these two vancomycin dosing strategies in children are clearly needed to validate these findings.
比较基于体重、身高或体表面积（BSA）的替代万古霉素剂量策略在实现儿童和青少年整个体型分布的等比万古霉素血清浓度-时间曲线下面积（AUC）值方面的可能性。
使用回顾性收集的病历数据进行最大后验概率贝叶斯（MAP-Bayesian）药代动力学分析。
儿童医院。
共 115 名年龄在 1-20 岁之间、在重症监护室外接受万古霉素治疗的患者，他们在 2011 年 5 月 1 日至 2012 年 8 月 31 日期间接受了治疗，并且至少有两次万古霉素血清浓度测量。
从患者的病历中提取万古霉素剂量和浓度-时间信息以及与肾功能估计相关的人口统计学和实验室数据。使用之前建立的单室模型，为每位患者推导出 MAP-Bayesian 估计的药代动力学系统参数。事后线性和幂函数回归用于比较清除率（Cl）和中央室分布容积（Vc）与体型描述符（体重、身高和 BSA）。评估了体型描述符索引参数在整个体型分布中的关系。估计了基于体重、身高和 BSA 的万古霉素剂量方案与 AUC24 值的关系。
115 名患者（56.5%为男性）的平均年龄±标准差、身高和体重分别为 9.7±5.4 岁、133±32.3cm 和 38.0±24.2kg。每个患者至少接受了 4 剂万古霉素治疗，并且有 2 到 9 次血清万古霉素浓度测量，所有患者共进行了 313 次测量。万古霉素 Cl 是体重的非线性函数，是 BSA 的线性比例函数，而中央室分布容积（Vc）是体重的线性比例函数。体重为 60-70mg/kg/天的万古霉素基于体重的剂量，预计 AUC24 值的中位数（第 5 至 95 百分位数）分别为 446（315-834）mg·h/L 和 649（385-1165）mg·h/L，体重小于 40kg（n=72）和体重为 40kg 或更重（n=43）的患者。相比之下，BSA 为基础的剂量方案在整个体型分布中更有可能实现等比 AUC24 值。
BSA 为基础的万古霉素剂量方案比基于体重（mg/kg）的剂量方案更有可能在儿童和青少年整个体型分布中实现等比 AUC24 值。显然需要进行比较这两种万古霉素剂量策略的药代动力学研究，以验证这些发现。
