Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Department of Surgery and Morphomic Analysis Group, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.01402-17. Print 2017 Nov.
Antibiotics such as vancomycin are empirically dosed on the basis of body weight, which may not be optimal across the expanding adult body size distribution. Our aim was to compare the relationships between morphomic parameters generated from computed tomography images to conventional body size metrics as predictors of vancomycin pharmacokinetics (PK). This single-center retrospective study included 300 patients with 1,622 vancomycin concentration (52% trough) measurements. Bayesian estimation was used to compute individual vancomycin volume of distribution of the central compartment (Vc) and clearance (CL). Approximately 45% of patients were obese with an overall median (5th, 95th percentile) weight and body mass index of 87.2 (54.7, 123) kg and 28.8 (18.9, 43.7) kg/m, respectively. Morphomic parameters of body size such as body depth, total body area, and torso volume of the twelfth thoracic through fourth lumbar vertebrae (T12 to L4) correlated with Vc. The relationship of vancomycin Vc was poorly predicted by body size but was stronger with T12-to-L4 torso volume (coefficient of determination [] = 0.11) than weight ( = 0.04). No relationships between vancomycin CL and traditional body size metrics could be discerned; however, relationships with skeletal muscle volume and total psoas area were found. Vancomycin CL independently correlated with total psoas area and inversely correlated with age. Thus, vancomycin CL was significantly related to total psoas area over age ( = 0.23, < 0.0001). This proof-of-concept study suggests a potential role for translation of radiographic information into parameters predictive of drug pharmacokinetics. Prediction of individual antimicrobial pharmacokinetic parameters using analytic morphomics has the potential to improve antimicrobial dose selection and outcomes of obese patients.
抗生素（如万古霉素）是根据体重经验性给药的，但在不断扩大的成人体型分布中，这种方法可能并不理想。我们的目的是比较 CT 图像生成的形态参数与传统体型指标作为预测万古霉素药代动力学（PK）的指标之间的关系。这项单中心回顾性研究纳入了 300 名患者，共进行了 1622 次万古霉素浓度（52%谷值）测量。贝叶斯估计用于计算万古霉素中央室分布容积（Vc）和清除率（CL）的个体值。约 45%的患者肥胖，体重和体重指数的总体中位数（第 5 百分位数，第 95 百分位数）分别为 87.2（54.7，123）kg 和 28.8（18.9，43.7）kg/m2。体型的形态学参数，如身体深度、全身表面积和第十二胸椎到第四腰椎（T12 到 L4）的躯干体积，与 Vc 相关。万古霉素 Vc 与体型的关系较差，但与 T12 到 L4 躯干体积的关系（决定系数 []=0.11）强于体重（ =0.04）。万古霉素 CL 与传统体型指标之间没有关系；然而，与骨骼肌体积和总腰大肌面积有关。万古霉素 CL 与总腰大肌面积独立相关，与年龄呈负相关。因此，万古霉素 CL 与年龄相关的总腰大肌面积显著相关（ =0.23，<0.0001）。这项概念验证研究表明，将放射学信息转化为预测药物药代动力学的参数具有潜在作用。使用分析形态学预测个体抗菌药物药代动力学参数有可能改善肥胖患者的抗菌药物剂量选择和结局。
