Background

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.

Objective

The objective of this study is to assess the correlational fit between vancomycin population-predicted and patient-specific pharmacokinetic parameters [elimination rate constant (K_e) and half-life (t_1/2)] in a case series of adult hospitalized patients.

Methods

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/m² 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.

Results

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_e and t_1/2 using all four creatinine clearance estimation methods were each significantly correlated with patient-specific K_e and t_1/2 (all Pearson correlation coefficients [r]: > + 0.7, p < 0.001). The population-predicted K_e and t_1/2 calculated using Cockcroft–Gault creatinine clearance using adjusted body weight showed the strongest association with patient-specific K_e and t_1/2. In the subgroup analyses, all the population-predicted K_e and t_1/2 using four creatinine clearance estimation methods were each significantly correlated with patient-specific K_e and t_1/2. The exception was the population-predicted t_1/2 derived from Cockcroft–Gault creatinine clearance using actual body weight that did not show a significant correlation with patient-specific t_1/2 in obese patients.

Conclusions

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.

中文翻译：

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在成人住院患者中万古霉素人群预测的药代动力学与患者特定的药代动力学的一致性：一个病例系列。

背景

万古霉素经验疗法通常使用根据人群预测的药代动力学参数进行调整的临床算法进行给药。但是，可以使用患者特定的药代动力学计算设计万古霉素的精确剂量。

目的

这项研究的目的是评估在一系列成年住院患者中，万古霉素人群预测的和患者特定的药代动力学参数[消除率常数（K _e）和半衰期（t _1/2）]之间的相关性拟合。

方法

这是一个接受万古霉素治疗的住院成年患者的单中心病例系列，进行了肌酐清除率计算以推算人群预测的药代动力学参数，并使用两个万古霉素浓度来计算患者特异性的药代动力学参数。该病例系列的主要目的是评估人群预测的和患者特定的药代动力学参数之间的相关性。这项研究的次要目标是评估人群预测的和患者特定的药代动力学参数之间的平均偏差和精确度，以及评估特殊人群中人群预测的和患者特定的药代动力学参数之间的相关性（肥胖的患者指数≥30 kg / m ²和肾功能不全的患者）。所有相关分析均使用多种估计肾功能的方法（Salazar–Corcoran和Cockcroft–Gault方法，使用理想体重，实际体重或调整后的体重）对人群预测的药代动力学进行。所有显着性检验的α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。

结果

共有30名患者被纳入研究。肥胖的患者为33.3％（10/30），肾功能不全的患者为56.7％（17/30）。在研究的所有患者中，使用所有四种肌酐清除率估计方法计算出的人群预测的K _e和t _1/2均与患者特异性K _e和t _1/2显着相关（所有Pearson相关系数[ r ]： > + 0.7，p  <0.001）。人口预测的K _e和t _1/2用体重调整后的Cockcroft-Gault肌酐清除率计算得出的结果与患者特定的K _e和t _1/2密切相关。在亚组分析中，使用四种肌酐清除率估计方法对所有人群预测的K _e和t _1/2均与患者特异性K _e和t _1/2显着相关。唯一的例外是人口预测的t _1/2来自使用实际体重的Cockcroft-Gault肌酐清除率，与患者特定的t _1/2没有显着相关性。 在肥胖患者中。

结论

在这种情况下，人群预测的药代动力学参数与患者特定的药代动力学参数密切相关。万古霉素人群预测的药代动力学公式可以安全地用于预测患者的万古霉素药代动力学特征，并且可以在各种住院成年患者中作为经验给药策略加以维持。