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. 2023 Mar 30:11:1093171.
doi: 10.3389/fped.2023.1093171. eCollection 2023.

Population pharmacokinetics of vancomycin in very low birth weight neonates

Abdullah Alsultan  1 , Manea Fares Al Munjem  2 , Khulood Mohammed Atiq  3 , Zekra Kamel Aljehani  4 , Hessa Al Muqati  5 , Abdullah Almohaizeie  6 , Dalia Ahmed Ballal  7 , Tahani Makki Refaei  7 , Majed Al Jeraisy  5   8   9 , Abdulmohsen Assiri  7 , Manal Abouelkheir  10
Affiliations

Population pharmacokinetics of vancomycin in very low birth weight neonates

Abdullah Alsultan et al. Front Pediatr. .

Abstract

Introduction: Vancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates.

Methods: This multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0-24 of 400-600 or 400-800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL.

Results: In total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr).

Discussion: We developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.

Keywords: infectious disease; pharmacodynamic; pharmacokenetics; vancomycin; very low birth weigh neonates.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Correlation between covariates and Cl. Top figure is correlation between PMA and Cl normalized by bodyweight, bottom figure is correlation between Scr and Cl normalized by bodyweight.
Figure 2
Figure 2
Diagnostic plot for observed concentrations vs. predicted concentrations, figure on left is population predictions, figure on right is individual predictions.
Figure 3
Figure 3
Population weighed residuals (top left), individual weighed residuals plot (top right) and normalized prediction distribution error plot (bottom left) for the final population pharmacokinetic model.
Figure 4
Figure 4
Qq plot and histogram of the individual weighed residuals (left) and normalized prediction errors (right).
Figure 5
Figure 5
Visual predictive check (VPC) of our final model applied to the validation data set. The solid lines represent the 10th, 50th and 90th percentiles of observed data. The shaded regions represent the 90% confidence interval around the 10th, 50th and 90th percentiles of simulated data. The circles are observed concentrations.
Figure 6
Figure 6
Normalized prediction distribution error (NPDE) plot of our final model applied to the validation data set.
See this image and copyright information in PMC

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