Population Pharmacokinetic Models of Vancomycin in Paediatric Patients: A Systematic Review.

摘要: BACKGROUND Vancomycin is commonly used to treat gram-positive bacterial infections in the paediatric population, but dosing can be challenging. Population pharmacokinetic (popPK) modelling improve individualization of regimens. The primary objective this study was describe popPK models vancomycin and factors that influence (PK) variability patients. METHODS Systematic searches were conducted Cochrane Central Register Controlled Trials, MEDLINE, EMBASE, International Pharmaceutical Abstracts grey literature without language or publication status restrictions from inception 17 August 2020. Observational studies described development patients (< 18 years age) included. Risk bias assessed using National Heart, Lung Blood Institute Study Quality Assessment Tool for Case Series Studies. RESULTS Sixty-four observational (1 randomized controlled trial, 13 prospective 50 retrospective 9019 with at least 25,769 serum concentrations) mean age 2.5 years (range 1 day-18 years), creatinine 47.1 ± 33.6 µmol/L, estimated clearance 97.4 ± 76 mL/min/1.73m2. Most found PK best by a one-compartment model (71.9%). There wide range volume distribution (Vd) values 0.014-0.27 L/kg/h 0.43-1.46 L/kg, respectively) interindividual as high 49.7% 136% Vd, proportional residual up 37.5% additive 17.5 mg/L. most significant covariates weight, age, clearance, weight Vd. Variable recommendations suggested. CONCLUSION Numerous derived, however external validation suggested regimens analyses subgroup populations such dialysis are still needed before predictive performance applied recommendations. Significant intraindividual present, which demonstrated need ongoing therapeutic drug monitoring derivation certain populations,