Population Pharmacokinetic of vancomycin administered by continuous infusion in critically ill patients.

Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes. to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions. The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance Cr-Cl) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset. A one-compartment model (Volume of distribution; Vd, Elimination from compartement; Ke) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed anegative correlation between CLv and the severity of the renal impairment. The Internal validation of the final model showed that the plot of individual predicted concentration versus observed concentration resulted in r² = 0.86 in the final model.The external validation of the final model showed an acceptable predictive performance. We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the therapeutic target range which is critical in optimizing the efficacy and safety of this antibiotic.

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S. Karger AG, Basel.