Development of a Population Pharmacokinetic Model of Vancomycin and its Application in Chinese Geriatric Patients with Pulmonary Infections

BACKGROUND: The optimal use of vancomycin in the elderly requires information about the drug’s pharmacokinetics and the influence of various factors on the drug’s disposition. However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in elderly patients. OBJECTIVE: This study was conducted to estimate the population pharmacokinetics of vancomycin in Chinese geriatric patients (age ≥ 65 years) with pulmonary infections and to explore the clinical application of this information for vancomycin dose individualization. METHODS: The steady-state trough concentrations were retrospectively collected from January 2011 to December 2016 and were analyzed using the nonlinear mixed-effect model software. The final model was evaluated using the bootstrap method, goodness-of-fit plots and the normalized prediction distribution error method. MAIN OUTCOME MEASURE: Model parameters and prediction error. RESULTS: A total of 125 steady-state trough concentrations from 70 patients were retrospectively collected. A one-compartment model was established. The final model was depicted as clearance (CL) [L/h] = 2.45 × (CL(CR)/56.28) × 0.542; volume of distribution (V(d)) [L] = 154. The creatinine clearance (CL(CR)) was identified as the most significant covariate in the final model. The typical values of CL and V(d) in the final model were 2.45 L/h and 154 L, respectively. Model validation outcomes showed that the final model was stable and had satisfactory prediction performance. CONCLUSION: A population pharmacokinetic model was established to estimate the pharmacokinetics characteristics of Chinese geriatric patients with pulmonary infections, and this model can be used to develop an initial vancomycin dosing regimen for geriatric patients.