Concordance of Vancomycin Population-Predicted Pharmacokinetics with Patient-Specific Pharmacokinetics in Adult Hospitalized Patients: A Case Series

万古霉素群体预测药代动力学与成人住院患者个体药代动力学的一致性:病例系列研究

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Abstract

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/m(2) 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.

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