• Int. J. Antimicrob. Agents · Dec 2019

    Determination of optimal loading and maintenance doses for continuous infusion of vancomycin in critically ill patients: Population pharmacokinetic modelling and simulations for improved dosing schemes.

    • Dinh H Vu, Duy A Nguyen, Isabelle K Delattre, Trong T Ho, Hong G Do, Hong N Pham, Xuan C Dao, Nhan T Tran, Gia B Nguyen, Françoise Van Bambeke, Paul M Tulkens, and Hoang A Nguyen.
    • National Drug Information and Adverse Drug Reaction Monitoring Center, Hanoi University of Pharmacy, Hanoi, Vietnam. Electronic address: vudinhhoa@gmail.com.
    • Int. J. Antimicrob. Agents. 2019 Dec 1; 54 (6): 702-708.

    ObjectivesDespite extensive clinical use, limited data are available on optimal loading and maintenance doses of vancomycin in critically ill patients. This study aimed to develop a rational approach for optimised dosage of vancomycin given in a continuous infusion in critically ill patients.MethodsVancomycin pharmacokinetic (PK) data (total serum concentrations) were obtained from 55 intensive care unit (ICU) patients (Bach Mai Hospital, Hanoi, Vietnam) receiving a 20 mg/kg loading dose followed by continuous infusion stratified by creatinine clearance (CLCr). Population PK modelling and Monte Carlo simulations were performed using a nonlinear mixed-effects modelling (NONMEM) program for a target of 20-30 mg/L to optimise efficacy and minimise nephrotoxicity.ResultsA two-compartment model with first-order elimination best fitted the PK data with central and peripheral volumes of distribution of 1.01 and 2.39 L/kg, respectively (allometric scaling to a 70 kg standard subject). The population total clearance of 3.63 L/h was only explained by renal function in the covariate and final model. The simulations showed that a 25-mg/kg loading dose infused over 90 minutes was optimal to reach the target range. The optimal maintenance dose for low renal function (CLCr < 45 mL/min) was 1000-1500 mg/day. For augmented renal clearance (CLCr > 130 mL/min) the dose should be up to 3500 mg/day or even 4500 mg/day to achieve adequate exposure. These simulated maintenance doses were larger than previously proposed for non-ICU patients.ConclusionLarge loading and maintenance doses of vancomycin are generally needed in critically ill patients. Because of high interindividual variability in vancomycin PK, drug monitoring may still be necessary.Copyright © 2019 Elsevier Ltd. All rights reserved.

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