Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Antimicrob Agents Chemother. 2018 May 25;62(6). doi: 10.1128/AAC.00441-18. Print 2018 Jun.
A consistent approach to the dosing of aminoglycosides across the modern body size distribution has been elusive. We evaluated whether radiologically derived measures of body composition could explain more of the interpatient variability in aminoglycoside pharmacokinetics (PK) than standard body size metrics. This retrospective study included adult patients treated with gentamicin or tobramycin with at least three drug concentrations and computed tomography (CT) imaging available. Aminoglycoside volume and clearance (CL) estimates were computed using a two-compartment model by Bayesian analysis. Morphomic data were extracted from CT images using a custom algorithm. Bivariable and multivariable linear regression were used to assess relationships between PK parameters and covariates. A total of 335 patients were included with a median (minimum, maximum) of 4 (3, 16) aminoglycoside concentrations per patient. The median (minimum, maximum) age, height, and weight of included patients were 57 (21, 93) years, 170 (145, 203) centimeters, and 81 (42, 187) kilograms. Both standard and morphomic measures poorly explained variability in volume ( < 0.06). Skeletal muscle area and volume explained more of the interpatient variability in CL than weight or sex. Higher precision was observed using a modified Cockcroft-Gault equation with skeletal muscle area at L3 ( 0.38) or L4 ( 0.37) than the standard Cockcroft-Gault equation using lean ( 0.23), adjusted ( 0.23), or total ( 0.22) body weights. These results highlight that skeletal muscle measurements from CT images obtained in the course of care can improve the precision of aminoglycoside CL estimation over current body size scalars.
在现代人体尺寸分布中，氨基糖苷类药物的剂量一直难以确定。我们评估了放射学衍生的身体成分测量值是否比标准身体尺寸指标能更好地解释氨基糖苷类药物药代动力学（PK）的个体间变异性。这项回顾性研究包括接受庆大霉素或妥布霉素治疗且至少有 3 个药物浓度和计算机断层扫描（CT）成像的成年患者。使用贝叶斯分析的两室模型计算氨基糖苷类药物的体积和清除率（CL）估计值。使用定制算法从 CT 图像中提取形态数据。使用双变量和多变量线性回归评估 PK 参数与协变量之间的关系。共纳入 335 例患者，每名患者的平均（最小，最大）氨基糖苷类药物浓度为 4（3，16）个。纳入患者的平均（最小，最大）年龄、身高和体重分别为 57（21，93）岁、170（145，203）厘米和 81（42，187）千克。标准和形态学测量均无法很好地解释体积的变异性（ < 0.06）。骨骼肌面积和体积比体重或性别更能解释 CL 的个体间变异性。与使用瘦体重（ 0.23）、调整体重（ 0.23）或总体重（ 0.22）的标准 Cockcroft-Gault 方程相比，使用第 3 腰椎（L3）或第 4 腰椎（L4）的骨骼肌面积的改良 Cockcroft-Gault 方程观察到更高的精度（ 0.38）或（ 0.37）。这些结果表明，在治疗过程中从 CT 图像获得的骨骼肌测量值可以提高氨基糖苷类药物 CL 估计的精度，优于当前的身体尺寸标度。
