Drugs in R&D (Mar 2020)

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

  • IfeanyiChukwu O. Onor,
  • Alison Neuliep,
  • Kieu Anh Tran,
  • Jennifer Lambert,
  • Christopher J. Gillard,
  • Fatima Brakta,
  • Michael C. Ezebuenyi,
  • Kirbie St. James,
  • John I. Okogbaa,
  • Robbie A. Beyl

DOI
https://doi.org/10.1007/s40268-020-00298-0
Journal volume & issue
Vol. 20, no. 2
pp. 83 – 93

Abstract

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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/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 + 0.7, 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.