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. 2019 Mar-Apr;24(2):107-116.
doi: 10.5863/1551-6776-24.2.107.

Population Pharmacokinetics of Vancomycin in the Pediatric Cardiac Surgical Population

Brady S Moffett, Karla Resendiz, Jennifer Morris, Ayse Akcan-Arikan, Paul A Checchia

Population Pharmacokinetics of Vancomycin in the Pediatric Cardiac Surgical Population

Brady S Moffett et al. J Pediatr Pharmacol Ther. 2019 Mar-Apr.

Abstract

Objective: Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing.

Methods: A retrospective, population pharmacokinetic study was performed for patients <19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011-2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC0-24:MIC (minimum inhibitory concentration) ratio of >400.

Results: A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07-0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4-14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC0-24:MIC ratio > 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L.

Conclusions: Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy.

Keywords: NONMEM; cardiac surgery; pediatrics; population pharmacokinetics; simulation; vancomycin.

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Conflict of interest statement

Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data and take responsibility for the integrity and accuracy of the data analysis.

Figures

Figure 1.
Figure 1.
Vancomycin serum concentrations versus time after a vancomycin dose.
Figure 2.
Figure 2.
Dependent variables versus population-predicted concentrations. There is agreement along the line of unity.
Figure 3.
Figure 3.
Dependent variables versus individual-predicted concentrations.
Figure 4.
Figure 4.
Conditional weighted residuals versus predicted values. There is no apparent bias.
Figure 5.
Figure 5.
Conditional weighted residuals versus time after dose. There is no apparent bias.
See this image and copyright information in PMC

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