Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient

Moffett, Brady S.; Ivaturi, Vijay; Morris, Jennifer; Akcan-Arikan, Ayse; Dutta, Ankhi

doi:10.1128/aac.02359-18

Cited by 11 publications

(11 citation statements)

References 11 publications

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“…An analysis by Lanke et al in 463 adolescents aged 12-18 years found that vancomycin clearance increased with TBW and creatinine clearance based on the bedside Schwartz equation, similar to our results (25). Another study in 196 mostly adolescent overweight and obese children found that besides serum creatinine, fat-free mass best predicted vancomycin clearance (26). In their dataset, total body weight could not be identified as a predictor of clearance.…”

Section: Discussionsupporting

confidence: 82%

“…There is currently a limited number of vancomycin pharmacokinetic studies that have been performed in obese children or adolescents (18,19,(24)(25)(26)(27). In contrast to our study, the majority of these publications lack specific dose recommendations, in particular regarding the combination of renal impairment and obesity.…”

Section: Discussionmentioning

confidence: 65%

“…The limited number of pharmacokinetic studies conducted has proposed different covariates for vancomycin clearance in obese children and adolescents. Among others, body size descriptors like total body weight (TBW), body surface area (BSA), or fat-free mass (FFM), age, or parameters representing the renal function such as serum creatinine or creatinine clearance (CL cr ) have been suggested (24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

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Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Smit

Goulooze

Brüggemann³

et al. 2021

AAPS J

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Vancomycin is an effective but potentially nephrotoxic antibiotic commonly used for severe infections. Dosing guidelines for vancomycin in obese children and adolescents with or without renal impairment are currently lacking. This study describes the pharmacokinetics of vancomycin in a large pediatric cohort with varying degrees of obesity and renal function to design practical dosing guidelines for this population. A multi-center retrospective population pharmacokinetic study was conducted using data from patients aged 1−18 years who received >1 dose of vancomycin and had ≥1 vancomycin concentration measured between January 2006 and December 2012. Besides pharmacokinetic data, age, gender, body weight, creatinine clearance (CLcr, bedside Schwartz equation), ward, race, and neutropenic status were collected. Population pharmacokinetic analysis and simulations were performed using NONMEM7.4. A total of 1892 patients (5524 samples) were included, with total body weight (TBW) ranging 6−188 kg (1344 normal weight, 247 overweight, and 301 obese patients) and CLcr down to 8.6 mL/min/1.73 m2. The two-compartment model, with clearance (CL) significantly increasing with TBW and CLcr, central and peripheral volume of distribution and inter-compartmental clearance increasing with TBW, performed well for all age, weight, and renal function ranges. A dosing guideline is proposed that integrates body weight and CLcr resulting in effective and safe exposures across all ages, body weight, and renal functions in the pediatric population. We have characterized the full pharmacokinetic profile of vancomycin in obese children and adolescents aged 1−18 years and propose a practical dosing guideline that integrates both body weight and renal function.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Smit

Goulooze

Brüggemann³

et al. 2021

AAPS J

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“…WT was identified as a major covariate describing the change in CL of vancomycin in the kidney transplant recipients in postoperative period. WT and body mass index (BMI) have been identified as a risk factor for potentially suboptimal serum concentration of vancomycin in patients ( Crass et al, 2018 ; Moffett et al, 2019 ; Smit et al, 2019 ). It has also been reported that the CL and V of vancomycin are related to WT and body sizes ( Pai et al, 2017 ; Dunn et al, 2019 ; Pokorná et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Vancomycin in Kidney Transplant Recipients: Model Building and Parameter Optimization

Liu

Jiao

et al. 2020

Front. Pharmacol.

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Background: Depending on the renal function of patients and many other influencing factors, studies on vancomycin pharmacokinetics show significant inter-and intraindividual variability. The present study was conducted using a population pharmacokinetics method to investigate the pharmacokinetic parameters and identified their influencing covariates for intravenous vancomycin in adult kidney transplant recipients. Methods:The drug monitoring data included 56 adult renal transplant recipients who received intravenous vancomycin as prophylactic medication. The analysis was performed by a population approach with NONMEM. Data were collected mainly during the first week after transplantation. Monitoring of vancomycin trough concentration in blood was initiated mainly 3-5 days after the initial administration. Results:The one-compartment open model was optimal and adequately described the data. Body weight (WT) and estimated glomerular filtration rate (GFR) were identified as significant covariates of the pharmacokinetic parameters CL and V of intravenous vancomycin in the kidney transplant patients. The typical values of vancomycin CL and V were 2.08 L h -1 and 63.2 L, respectively. A dosage strategy scheme according to model results was also designed. Conclusion:Both WT and GFR of the kidney transplant patients positively influence the pharmacokinetic parameters CL and V for intravenous vancomycin. Our population

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“…A total of 10 models were reviewed (Figure 1), among which eight models were one-compartment models with first-order elimination, and the remaining two models were two-compartment models with first-order elimination, to describe the pharmacokinetic parameters of vancomycin. [19][20][21][22][23][24][25][26][27][28] Weight was retained as a covariate in 10 models, one of which used a fat-free mass index.…”

Section: Review Of the Published Poppk Modelsmentioning

confidence: 99%

Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents

et al. 2021

J Clin Pharm Ther

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What is known and objectives: Various population pharmacokinetic (PopPK) models for vancomycin in children and adolescents have been constructed to optimize the therapeutic regimen of vancomycin. However, little is known about their predictive performance when extrapolated to different clinical centres. Therefore, the aim of this study was to externally validate the predictability of vancomycin PopPK model when extrapolated to different clinical centres and verify its applicability in an independent data set. Methods:The published models were screened from the literature and evaluated using an external data set of a total of 451 blood concentrations of vancomycin measured in 220 Chinese paediatric patients. Prediction-and simulation-based diagnostics and Bayesian forecasting were performed to evaluate the predictive performance of the models.Results: Ten published PopPK models were assessed. Prediction-based diagnostics showed that none of the investigated models met all the standards (median prediction error (MDPE) ≤ ±20%, median absolute prediction error (MAPE) ≤30%, PE% within ±20% (F 20 ) ≥35% and PE% within ±30% (F 30 ) ≥50%), indicating unsatisfactory predictability. In simulation-based diagnostics, both the visual predictive checks (VPC) and the normalized prediction distribution error (NPDE) indicated misspecification in all models. Bayesian forecasting results showed that the accuracy and precision of individual predictions could be significantly improved with one or two prior observations, but frequent monitoring might not be necessary in the clinic, since Bayesian forecasting identified that greater number of samples did not significantly improve the predictability. Model 3 established by Moffett et al showed better predictability than other models. What is new and conclusion:The 10 published models performed unsatisfactorily in prediction-and simulation-based diagnostics; none of the published models was | 821 LV et aL. How to cite this article: Lv C, Lu J, Jing L, et al. Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents. J

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Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient

Cited by 11 publications

References 11 publications

Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Population Pharmacokinetics of Vancomycin in Kidney Transplant Recipients: Model Building and Parameter Optimization

Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents

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