College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, Box COP, New Orleans, LA, 70125, USA.
Department of Medicine, Louisiana State University Health Sciences Center School of Medicine, 1542 Tulane Avenue, New Orleans, LA, 70112, USA.
Drugs R D. 2020 Jun;20(2):83-93. doi: 10.1007/s40268-020-00298-0.
Vancomycin empiric therapy is commonly dosed using clinical algorithms adapted from population-predicted pharmacokinetic parameters. However, precise dosing of vancomycin can be designed using patient-specific pharmacokinetic calculations.
The objective of this study is to assess the correlational fit between vancomycin population-predicted and patient-specific pharmacokinetic parameters [elimination rate constant (K) and half-life (t)] in a case series of adult hospitalized patients.
This is a single-center case series of hospitalized adult patients who received vancomycin, had creatinine clearance calculation for derivation of population-predicted pharmacokinetic parameters, and had two vancomycin concentrations for calculation of patient-specific pharmacokinetic parameters. The primary objective of this case series is to evaluate the correlation between population-predicted and patient-specific pharmacokinetic parameters. The secondary objectives of this study are to evaluate the mean bias and precision between the population-predicted and patient-specific pharmacokinetic parameters and to assess the correlation between population-predicted and patient-specific pharmacokinetic parameters in special population subgroups (obese patients with body mass index ≥ 30 kg/m and patients with renal dysfunction). All correlation analyses were performed on the population-predicted pharmacokinetics using diverse methods of estimating renal function (Salazar-Corcoran and Cockcroft-Gault methods using either ideal, actual, or adjusted body weights). All significance testing was set at an α of < 0.05. IBM SPSS Statistics version 25 and SAS version 9.4 were used to conduct all statistical analyses.
A total of 30 patients were included in the study; 33.3% (10/30) of the patients were obese and 56.7% (17/30) had renal dysfunction. In all patients in the study, the calculated population-predicted K and t using all four creatinine clearance estimation methods were each significantly correlated with patient-specific K and t (all Pearson correlation coefficients [r]: > + 0.7, p < 0.001). The population-predicted K and t calculated using Cockcroft-Gault creatinine clearance using adjusted body weight showed the strongest association with patient-specific K and t. In the subgroup analyses, all the population-predicted K and t using four creatinine clearance estimation methods were each significantly correlated with patient-specific K and t. The exception was the population-predicted t derived from Cockcroft-Gault creatinine clearance using actual body weight that did not show a significant correlation with patient-specific t in obese patients.
In this case series, population-predicted pharmacokinetic parameters were strongly correlated with patient-specific pharmacokinetic parameters. The vancomycin population-predicted pharmacokinetic formula can be used safely to predict a patient's vancomycin pharmacokinetic disposition and can be maintained as an empiric dosing strategy in various hospitalized adult patients.
万古霉素经验性治疗通常采用基于群体预测药代动力学参数的临床算法进行剂量调整。然而，通过患者特异性药代动力学计算可以精确设计万古霉素的剂量。
本研究旨在评估成人住院患者中万古霉素群体预测和患者特异性药代动力学参数[消除率常数（K）和半衰期（t）]的相关性。
这是一项单中心的成人住院患者病例系列研究，这些患者接受了万古霉素治疗，计算了肌酐清除率以推导出群体预测的药代动力学参数，并进行了两次万古霉素浓度检测以计算患者特异性药代动力学参数。该病例系列的主要目的是评估群体预测和患者特异性药代动力学参数之间的相关性。本研究的次要目的是评估群体预测和患者特异性药代动力学参数之间的平均偏差和精度，并评估特殊人群亚组（体重指数≥30 kg/m2的肥胖患者和肾功能不全患者）中群体预测和患者特异性药代动力学参数之间的相关性。使用不同的肾功能估计方法（使用理想、实际或调整后的体重的 Salazar-Corcoran 和 Cockcroft-Gault 方法）对所有群体预测药代动力学进行了所有相关性分析。所有显著性检验的 α 值均设置为<0.05。使用 IBM SPSS Statistics 版本 25 和 SAS 版本 9.4 进行所有统计分析。
共有 30 名患者纳入研究；33.3%（10/30）的患者为肥胖患者，56.7%（17/30）的患者存在肾功能不全。在研究中的所有患者中，使用所有四种肌酐清除率估计方法计算的群体预测 K 和 t 均与患者特异性 K 和 t 显著相关（所有 Pearson 相关系数[r]：均>+0.7，p<0.001）。使用调整后体重的 Cockcroft-Gault 肌酐清除率计算的群体预测 K 和 t 与患者特异性 K 和 t 的关联最强。在亚组分析中，使用四种肌酐清除率估计方法计算的所有群体预测 K 和 t 均与患者特异性 K 和 t 显著相关。例外的是，使用实际体重的 Cockcroft-Gault 肌酐清除率计算的群体预测 t 与肥胖患者的患者特异性 t 没有显著相关性。
在本病例系列中，群体预测药代动力学参数与患者特异性药代动力学参数密切相关。万古霉素群体预测药代动力学公式可安全用于预测患者的万古霉素药代动力学分布，并可作为各种住院成年患者的经验性给药策略。
