Population Pharmacokinetics Modeling of Vancomycin Among Chinese Infants With Normal and Augmented Renal Function

Abstract

There have been good amounts of population pharmacokinetics (PPK) models of vancomycin for Chinese pediatric patients, but none of them had a special focus on modeling infant population with different levels of renal function. Since renal function variability is prominent among infant population and the clearance (CL) of vancomycin is heavily related to renal excretion, it is important to establish precise PPK models based on individual renal function levels. We employed a PPK approach to develop three models of vancomycin in parallel for Chinese pediatric patients with normal renal function [estimated glomerular filtration rate (eGFR) between 30 and 86 ml/min/1.73 m2, Model 1], with augmented renal function (eGFR ≥ 86 ml/min/1.73 m2, Model 2), or with all levels of renal function (Model 3). Three one-compartment models with first-order elimination kinetics were established. The predictive ability of Model 1 and Model 2 among each certain population is comparable with that of Model 3 with no statistical difference. Our study revealed that among the infant population with augmented renal function, only body weight was included as a covariate, which indicated that for an infant whose eGFR ≥ 86 ml/min/1.73 m2, taking blood sample is not compulsory for predicting vancomycin blood concentration, which avoids unnecessary injury to vulnerable infants.

Vancomycin population pharmacokinetics analysis in Chinese paediatric patients with varying degrees of renal function and ages: development of new practical dosing recommendations

“…As illustrated in Figure 1 , an approximately linear correlation was only observed between vancomycin CL and eGFR below 120 mL/min/1.73 m 2 . This finding is in agreement with previous studies by Smit et al ., 27 Li et al ., 12 Lv et al . 36 and Yamamoto et al ., 37 who also reported that vancomycin CL was correlated with eGFR only in patients with normal or impaired renal function.…”

“…Previous studies have identified that WT and age are the critical variables that must be considered when establishing vancomycin PPK models for children, particularly for young infants. 12 Therefore, we evaluated these two covariates at first in a series of size and maturation models. 17 , 18 The maturation factor (MF), was used to describe the developmental contribution to CL.…”