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Vancomycin dosing in obesity in children – Vancomycin dosing in obese pediatric patients

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Matthew Cox
Thursday, March 25, 2021
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  • This study characterizes the population pharmacokinetics of vancomycin in a large, multi-center clinical population of normal weight, overweight, and obese children and adolescents, with varying renal function, to design practical dose recommendations for this population. Add comment Close comment form modal.

  • Results: We identified records. For Bayesian forecasting, the current PK model can be used as a basis.

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Paediatr Drugs. This is substantiated by a pediatric pharmacokinetic study with vancomycin, where a body weight-dependent exponent was found to be superior compared to a simple model with TBW as a covariate, since this study was done in non-obese children mostly under 1 year of age Although the principles of allometric scaling have been well established in predicting drug clearance in normal weight children over 5 years of age, this is not the case for obese children or children aged below 5 years

  • Obesity and pediatric drug development. Clin Chem.

  • Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. The lines show how clearance changes with body weight over the available weight range according to the final model for four typical values of CL cr i.

  • According to local clinical practice, vancomycin dosage and concentration measurements were left to the discretion of the treating physician.

  • The pvcVPC plots Fig.

  • Tracy M. To purchase short term access, please sign in to your Oxford Academic account above.

Skip Nav Destination Article Navigation. Results: We identified records. Am J Heal Pharm. Acknowledgements The authors like to acknowledge Mr.

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This finding is in agreement with our observations, showing that the IDSA and BNFc guidelines lead to increasing exposure and trough concentrations with increasing body weight to the point where the dose is being capped. As a last remark, we estimated an exponent of 0. View author publications. Vancomycin dosage in overweight and obese children. You have entered an invalid code. Supplementary Information. All payments were invoiced by the Radboud University Medical Centre.

The linear range for the assay was 1. Figure 1 shows the wide scatter in sampling time after dose for the three groups. Submit Cancel. Clin Pharmacokinet. Related articles in Web of Science Google Scholar. Context: Vancomycin is a medication with potential for significant harm with both overdosing and underdosing.

  • In this perspective, we did not only investigate the influence of body weight as a variable but also looked into more sophisticated models that separately characterize the influence of weight for age-and-length and weight excess following equation S8 in the supplementary file. It should be recognized that the performance of this equation in the obese pediatric population is uncertain

  • Lastly, vancomycin was given exclusively as intermittent infusions in the population included in our dataset.

  • Another study in mostly adolescent overweight and obese children found that besides serum creatinine, fat-free mass best predicted vancomycin clearance Final report of the Commission on Ending Childhood Obesity.

  • Comment title. Issue Section:.

Accepted : 03 March This study describes the pharmacokinetics of vancomycin in a large pediatric cohort with vancomycin dosing in obesity in children degrees of obesity and renal function to design practical dosing guidelines for this population. Don't already have an Oxford Academic account? More details regarding available covariates can be found in the supplementary file methods—pharmacokinetic analysis. Lastly, trough C min concentrations corresponding to the primary target were explored. In addition, TBW was the most significant covariate for central and peripheral volume of distribution and inter-compartment clearance. J Clin Pharmacol.

Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards vancomycin dosing in obesity in children semi-physiological function for maturation in glomerular dpsing. Human renal function maturation: a quantitative description using weight and postmenstrual age. There was a broad range in CL cr bedside Schwartz equation with values as low as 8. Accepted : 03 March Skip Nav Destination Article Navigation. Secondary objectives included a comparison of dosage changes and toxicities. Add comment Close comment form modal.

MeSH terms

Am J Heal Pharm. Predictive performance of a busulfan pharmacokinetic model in children and young adults. To do this, for each patient, body weight related to growth WT for age and length and excess body weight WT excess were calculated according to equations S1 and S2 in the supplementary file, adapted from Van Rongen et al. J Pharmacokinet Pharmacodyn. Nederlands Kenniscentrum voor Farmacotherapie bij Kinderen.

Receive exclusive offers and updates from Oxford Academic. Don't already have an Oxford Academic account? In contrast to our study, the majority of these publications lack specific dose recommendations, facility location problem definition of obesity particular regarding the combination of renal impairment and obesity. Search SpringerLink Search. To our best knowledge, the pediatric pharmacokinetics of vancomycin has not been described before in such a large and rich dataset, with a broad range and overlay of multiple relevant covariates such as age, body weight, and renal function and where the vancomycin samples showed a good distribution in time after dose, especially over the first 12 h. Clinical Growth Charts. Children are generally underrepresented during drug development trials, and, if children are included, often there is no active inclusion of obese children 7.

In contrast to our study, the majority of these publications lack specific dose recommendations, in particular regarding the combination of renal impairment and obesity. Pediatr Nephrol. Permissions Icon Permissions. Clin Infect Dis.

INTRODUCTION

Abstract Context: Vancomycin is a medication with potential for significant harm with both overdosing and underdosing. References 1. The pvcVPC plots Fig. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients.

Download all slides. Data on demographics, lab obesity children, and clinical PK data were extracted from the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31, Pediatric obesity: pharmacokinetics and implications for drug dosing. The variability in trough concentrations related to target exposure as a result of dosing frequency, age, or weight has been described before for several populations, including obese adults and normal weight children 2223 ,

This implies that for vancomycin clearance on children, there seems to be no difference in the influence of weight resulting from growth and development and excess weight resulting from obesity. Select Format Select format. Permissions Icon Permissions. Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration.

All rights reserved. Knibbe im that they have no conflicts of interest. Thank you for submitting a comment on this article. Improving the estimation of parameter uncertainty distributions in nonlinear mixed effects models using sampling importance resampling. This particularly applies to BNFc and IDSA guidelines, which do not recommend dose adjustments for patients with reduced renal function. Sign In.

INTRODUCTION

Jamie L. Am J Health Syst Pharm. The linear range for the assay was 1. This value is close to 0.

Issue Section:. Nederlands Kenniscentrum voor Farmacotherapie bij Kinderen. Data on demographics, lab values, and clinical PK data were extracted obesiy the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31, The study was reviewed and approved by the Intermountain Healthcare and University of Utah Institutional Review Boards, and a waiver of informed consent was granted. As for the use of weight in predicting clearance, it is important to realize that in pediatrics, weight can be a result of either growth reflecting age or excessive growth in obesity. Permissions Icon Permissions. Pharm Res.

The parameter precision of the structural and final vancomycjn was analyzed by the sampling importance resampling SIR procedure Download all slides. Patients were then stratified into two groups: normal-weight patients and overweight or obese patients. Most characteristics, including age and renal function, were similarly distributed across the three weight groups Table I. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Regarding renal function, we found that the use of the bedside Schwartz equation outperformed the use of serum creatinine or creatinine ratio for predicting vancomycin clearance.

Prediction-corrected observations are obesitty as dots, with the median, 2. Clin Chem. Ethics declarations Conflict of Interest No funding was received for this work. Download PDF. However, the authors state that the differences between obese and non-obese individuals are small and do not necessitate any dose adjustments. In light of these TDM recommendations, we show that trough concentrations may vary vastly, with values ranging from 7. Antimicrob Agents Chemother.

You do not currently have childen to this article. Abstract Purpose. A dosing guideline is proposed that integrates body weight and CL cr resulting in effective and safe exposures across all ages, body weight, and renal functions in the pediatric population. The study was reviewed and approved by the Intermountain Healthcare and University of Utah Institutional Review Boards, and a waiver of informed consent was granted.

The variability in trough concentrations related to target exposure as a result of dosing frequency, age, or weight has vancomycin dosing in obesity in children described before for several populations, including obese adults and normal weight children 2223 A study of prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses in milligrams per kilogram given to normal-weight children compared with overweight or obese children. The lines show how clearance changes with body weight over the available weight range according to the final model for four typical values of CL cr i. View Metrics. Outside of this work, he has served as a consultant to and has received unrestricted research grants from Astellas Pharma Inc. Data extraction: The primary outcome was vancomycin level.

Br J Clin Pharmacol. Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration. Assay validation was performed for clinical purposes. Ethics declarations Conflict of Interest No funding was received for this work. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Download citation. Therefore, readers should not use our results in children below 1 year of age for which we refer to other dosing guidelines

Misty Miller, Pharm. Population pharmacokinetics of vancomycin in obesity: childrne the optimal dose for morbidly obese individuals. Consequently, our dose recommendations must be used with extra caution for this subgroup. According to local clinical practice, vancomycin dosage and concentration measurements were left to the discretion of the treating physician. Predictive performance of a busulfan pharmacokinetic model in children and young adults.

Based on the final model in which the influence of both renal function and body weight on vancomycin clearance and weight on vancomycin dosing in obesity in children of distribution were quantified, we defined dosing recommendations for the pediatric population Table III. Submit a comment. The goodness-of-fit and validity of the model were confirmed by goodness-of-fit plots Figure S1supplementary file and NPDE Figure S2supplementary file. The two-compartment model, with clearance CL significantly increasing with TBW and CL crcentral and peripheral volume of distribution and inter-compartmental clearance increasing with TBW, performed well for all age, weight, and renal function ranges. The authors like to acknowledge Mr. Children under 1 year of age were excluded from this study.

Our study clearly shows that dose adjustments are however necessary to prevent subtherapeutic or toxic exposures. Skip Nav Destination Article Navigation. Knibbe Authors Cornelis Smit View author publications. Vancomycin trough concentrations in overweight or obese pediatric patients. Donald Harrison, Ph. Obesity may affect vancomycin pharmacokinetics and is increasingly common among children. Hagemann, Pharm.

In eosing study, we provide a practical dosing guideline for children and adolescents with varying levels of obesity and renal function based on a thorough characterization obesity children the vancomycin pharmacokinetics in a large pediatric and adolescent population aged 1—18 years that consists of normal weight, overweight, and obese individuals with a wide range of renal functions. Publication types Review Research Support, N. It has been well established that vancomycin efficacy and nephrotoxicity closely relate to the h area under the curve AUC 24 in relation to the minimal inhibitory concentration MIC Table I Baseline Characteristics Full size table. Download references.

Vancomycin trough concentrations in overweight or obese pediatric patients. Reprints and Permissions. However, despite its extensive use, there is cosing date limited data on how to tailor the dose in obese children and adolescents 13 Vancomycin clearance can be well predicted using a combination of CL cr using the bedside Schwartz equation and total body weight. Hence, our data indicates that even though overweight or obese children might show some indication of hyperfiltration based on the Schwartz equation, this does not translate to an increased vancomycin clearance. Indian J Pharm Sci.

In addition, goodness-of-fit plots and several other vancomycin dosing in obesity in children diagnostics were considered. This is substantiated obexity a pediatric pharmacokinetic study with vancomycin, where a body weight-dependent exponent was found to be superior compared to a simple model with TBW as a covariate, since this study was done in non-obese children mostly under 1 year of age Barlow SE. Predictive performance of a busulfan pharmacokinetic model in children and young adults. Br J Clin Pharmacol. In addition, we could not identify a maturation model using a body weight—dependent exponent following equation S7 in the supplementary file for clearance.

The lines show how clearance changes with body weight over the available weight range according to the final model for four typical values of Vancomycin dosing in obesity in children cr i. To evaluate existing dosing guidelines and, if necessary, design a new guideline, concentration-time profiles were simulated for several typical individuals from the dataset with different ages, body weight, and renal functions using the ranges found across the dataset. Don't have an account? The study was reviewed and approved by the Intermountain Healthcare and University of Utah Institutional Review Boards, and a waiver of informed consent was granted.

Some limitations of our study should be addressed. Donald Harrison, Ph. In this study, we provide a practical ibesity guideline for children and adolescents with varying levels of obesity and renal function based on a thorough characterization of the vancomycin pharmacokinetics in a large pediatric and adolescent population aged 1—18 years that consists of normal weight, overweight, and obese individuals with a wide range of renal functions.

Obessity J Heal Pharm. Infigratinib Phosphate. Population pharmacokinetic assessment of vancomycin dosing in the large pediatric patient. Vancomycin dosage in overweight and obese children. These principles presumably also apply to obese children, although well-designed studies that explore this are scarce 56. Related articles in Web of Science Google Scholar. In addition, although we included patients with renal function ranging down to 8.

A study vancomycun prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses in milligrams per kilogram given to normal-weight children compared with overweight or obese children. Am J Health Syst Pharm. In their dataset, total body weight could not be identified as a predictor of clearance. Association between vancomycin trough concentration and area under the concentration-time curve in neonates.

There was a broad range in CL cr childrren Schwartz equation with values as low as 8. Consequently, our dose recommendations must be used with extra caution for this subgroup. To our best knowledge, the pediatric pharmacokinetics of vancomycin has not been described before in such a large and rich dataset, with a broad range and overlay of multiple relevant covariates such as age, body weight, and renal function and where the vancomycin samples showed a good distribution in time after dose, especially over the first 12 h.

Donald Harrison, Ph. Thank you for submitting a comment on this article. Smit, S. Full size image. For Bayesian forecasting, the current PK model can be used as a basis. Vancomycin dosing in obese pediatric patients.

Predictive performance of a busulfan pharmacokinetic model in children and young adults. Full size image. Our study clearly shows that dose adjustments are however necessary to prevent subtherapeutic or toxic exposures. Susana Chavez-Bueno, M. References 1.

Prediction and variability corrected visual predictive check pvcVPCsplit for a weight group, b age group, and c for renal function group based on bedside Schwartz. Some limitations of our study should be addressed. Evaluation of discharge prescribing after rescheduling of gabapentin as a controlled substance.

In both steps, models were compared using the objection function value OFVwhere lower values indicate a better fit. Dosingg selected all patients aged 1—18 years who had at least two vancomycin administrations, at least one vancomycin concentration measured, and at least one weight measurement registered between start and end of treatment with vancomycin. Hosp Pediatr. Clin Pediatr Phila.

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  • Final report of the Commission on Ending Childhood Obesity.

  • Cornelis Smit, Sebastiaan C.

  • Dosing adjustments were made based on therapeutic drug monitoring TDM blood samples which dosinb collected as part of routine medical care. The variability in trough concentrations related to target exposure as a result of dosing frequency, age, or weight has been described before for several populations, including obese adults and normal weight children 2223 ,

  • Data on demographics, lab values, and clinical PK data were extracted from the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31,

Advanced Search. The pvcVPC plots Fig. Sign In or Create an Account. Download citation. Data on demographics, lab values, and clinical PK data were extracted from the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31, The intraday and interday relative standard deviations ranged from 4. Add comment Cancel.

Download references. Lastly, Le et choldren. Data on demographics, lab values, and clinical PK data were extracted from the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31, Another study in mostly adolescent overweight and obese children found that besides serum creatinine, fat-free mass best predicted vancomycin clearance

Download citation. The goodness-of-fit and validity of the model were confirmed by goodness-of-fit plots Figure S1supplementary file and NPDE Figure S2supplementary file. Select Format Select format. Inserts show the same data for the time frame 0 to 12 h after the last dose.

Your comment will be reviewed and published at the journal's discretion. I agree to the terms and conditions. Vancomycin dosing in obesity in children do this, for each patient, body dozing related to growth WT for age and length and excess body weight WT excess were calculated according to equations S1 and S2 in the supplementary file, adapted from Van Rongen et al. It is unclear what explains these results, but it cannot be excluded that these findings are explained by the absence of adolescents with normal weight unlike the data of our study. Reference intervals for serum creatinine concentrations: assessment of available data for global application.

Issue Section:. For each individual, AUC in boldVancomycin dosing in obesity in children min at day 3, and AUC at day 1 are shown in the graph where color corresponds to the obfsity renal function. Data Collection Data on demographics, lab values, and clinical PK data were extracted from the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31, Over the past decades, the prevalence of childhood obesity has increased at an alarming rate. The goodness-of-fit and validity of the model were confirmed by goodness-of-fit plots Figure S1supplementary file and NPDE Figure S2supplementary file. Comment title.

Sign in Vabcomycin already have an Oxford Academic account? Antimicrob Agents Chemother. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. About this article. This particularly applies to BNFc and IDSA guidelines, which do not recommend dose adjustments for patients with reduced renal function.

In both steps, models were compared using the objection function value OFVwhere lower values indicate a better fit. View author publications. An analysis by Lanke et al. Dosint furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. According to local clinical practice, vancomycin dosage and concentration measurements were left to the discretion of the treating physician. Samples could be drawn within 30 min before the dose trough concentration30 min after the end of the intravenous infusion peak concentrationor at other time points.

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According to local clinical practice, vancomycin dosage and concentration measurements were left to the discretion of the treating physician. Permissions Icon Permissions. This retrospective study evaluated data for children who were age 2—17 years, received i. Clin J Am Soc Nephrol. For Bayesian forecasting, the current PK model can be used as a basis.

Conclusions: High-quality data to guide vancomycin dosing in children with obesity are lacking. About this article. Obesity may affect vancomycin pharmacokinetics and is increasingly common among children. In contrast to our study, the majority of these publications lack specific dose recommendations, in particular regarding the combination of renal impairment and obesity. Hence, for obese children and adolescents, current evidence suggests that the usual pediatric vancomycin dosages should be adjusted. Download all slides. Consequently, our dose recommendations must be used with extra caution for this subgroup.

All payments were invoiced by the Radboud University Medical Centre. Reprints and Permissions. Jamie L. Cornelis Smit, Sebastiaan C.

Am J Heal Pharm. A study of prescribing facility location problem definition of obesity in one hospital revealed no significant difference in vancomycun size of vancomycin doses in milligrams per kilogram given to normal-weight children compared with overweight or obese children. Clin Infect Dis. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Another study in mostly adolescent overweight and obese children found that besides serum creatinine, fat-free mass best predicted vancomycin clearance Table I Baseline Characteristics Full size table. Oxford Academic.

J Pharmacokinet Pharmacodyn. Submit Cancel. Download citation. Goulooze, C. Submit a comment.

In all these cases, the bedside Schwartz equation outperformed the other approaches in predicting vancomycin clearance. Clin Chem. Sign in via your Institution Sign in.

  • The pvcVPC plots Fig.

  • Improving the estimation of parameter uncertainty distributions in nonlinear mixed effects models using sampling importance resampling.

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Patients that received renal replacement therapy or extracorporeal membrane oxygenation during hospital admission were excluded from the analysis. The pvcVPC plots Fig. Accessed Sep This is not unexpected, since it is well-known that the maturation of renal excretion processes such as glomerular filtration rate GFR is nearly complete around 1 year of postnatal age Population pharmacokinetics of vancomycin in obesity: finding the optimal dose for morbidly obese individuals. Miller, Pharm. Dosing adjustments were made based on therapeutic drug monitoring TDM blood samples which were collected as part of routine medical care.

You vhildren also search for this author in PubMed Google Scholar. Paediatric Formulary Committee. The final model was internally validated by normalized prediction distribution errors NPDE and prediction and variability corrected visual predictive check pvcVPC. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. The details of the pharmacokinetic analysis can be found in the supplementary file methods—pharmacokinetic analysis.

In this perspective, we did not only investigate the influence of body weight as a variable but also looked into more sophisticated models that separately characterize the influence of weight for age-and-length and weight excess following equation S8 in the supplementary file. Accepted : 03 March In contrast to our study, the majority of these publications lack specific dose recommendations, in particular regarding the combination of renal impairment and obesity. Secondary objectives included a comparison of dosage changes and toxicities. Obesity and pediatric drug development. Figure 1 shows the wide scatter in sampling time after dose for the three groups.

Cite this article Smit, C. Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents. Misty Miller, Pharm. Consequently, our dose recommendations must be used with extra caution for this subgroup.

  • Hence, for obese children and adolescents, current evidence suggests that the usual pediatric vancomycin dosages should be adjusted.

  • You must accept the terms and conditions. Dosing of vancomycin in normal weight children has been investigated thoroughly

  • Vancomycin dosing in children and young adults: back to the drawing board.

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  • Another study in mostly adolescent overweight and obese children found that besides serum creatinine, fat-free mass best predicted vancomycin clearance Abstract Vancomycin is an effective but potentially nephrotoxic antibiotic commonly used for severe infections.

  • Improving the estimation of parameter uncertainty distributions in nonlinear mixed effects models using sampling importance resampling.

Prediction and variability corrected visual predictive check pvcVPCsplit for a weight group, b age group, and c for renal function group based on bedside Schwartz. Download all slides. Each dot represents one individual, with darker color representing a higher CL cr. Sign In Forgot password? As for the use of weight in predicting clearance, it is important to realize that in pediatrics, weight can be a result of either growth reflecting age or excessive growth in obesity. Cornelis Smit, Sebastiaan C. The intraday and interday relative standard deviations ranged from 4.

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You have childden an invalid code. None of these studies has reported on the relationship between trough concentrations and AUC 24which is relevant since trough concentrations are routinely measured while it is known that the relation between trough concentrations and AUC 24 depends on age and the dosing interval 22 Donald Harrison, Ph. Sign In or Create an Account. Download citation.

Abstract Purpose. Goulooze, C. The images or vancoomycin third party material in this article are included in the article's Creative Commons licence, vancomycin dosing in obesity in children indicated otherwise in a credit line to the material. You must accept the terms and conditions. This is substantiated by a pediatric pharmacokinetic study with vancomycin, where a body weight-dependent exponent was found to be superior compared to a simple model with TBW as a covariate, since this study was done in non-obese children mostly under 1 year of age This particularly applies to BNFc and IDSA guidelines, which do not recommend dose adjustments for patients with reduced renal function. All relevant baseline characteristics are shown in Table I.

Vancomycin is an effective but potentially nephrotoxic antibiotic commonly used for severe infections. The diagnostics of our final model show some slight underprediction of vancomycin concentrations in this group Figure S1supplementary filewhile the dose recommendations show that due to an increased elimination half-life, steady-state concentration has not been reached on day 3 in this patient group. You have entered an invalid code. Children under 1 year of age were excluded from this study. Miller, Pharm.

Handb Exp Pharmacol. For Bayesian forecasting, the current PK model can be used as a basis. Another study in mostly adolescent overweight and obese children found that children serum creatinine, fat-free mass best predicted vancomycin clearance If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. These simulations do not include remaining random variability, but as this variability is well-known for vancomycin, being the primary reason why vancomycin TDM is advised as part of standard practice 13we considered this random variability out of scope for the current manuscript.

Email alerts Article activity alert. Correspondence to Catherijne A. Conclusions: High-quality data to guide vancomycin dosing in children with obesity are lacking. Therefore, readers should not use our results in children below 1 year of age for which we refer to other dosing guidelines

Data were extracted by 2 reviewers. Reprints and Permissions. Clin J Am Soc Nephrol. The pharmacokinetic parameters of obesihy structural model without covariates are shown in Table II. Search SpringerLink Search. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Permissions Icon Permissions. The limited number of pharmacokinetic studies conducted has proposed vanconycin covariates for vancomycin clearance in obese children and adolescents. New issue alert. We selected all patients aged 1—18 years who had at least two vancomycin administrations, at least one vancomycin concentration measured, and at least one weight measurement registered between start and end of treatment with vancomycin. Indian J Pharm Sci.

Vancomycin is a glycopeptide antibiotic that is widely used in serious gram-positive infections including those with beta-lactam resistant Staphylococcus aureus and is known for its potential nephrotoxic side effects. Sign in Don't already have an Oxford Academic account? For Bayesian forecasting, the current PK model can be used as a basis. The simulations presented in this study serve the purpose to illustrate what can be expected in terms of vancomycin levels for different individuals including extremes in the target population when the new dosing guideline is used. Infigratinib Phosphate.

Download PDF. For Vancomycin dosing in obesity in children forecasting, the current PK model can be used as a basis. It is unclear what explains these results, but it cannot be excluded that these findings are explained by the absence of adolescents with normal weight unlike the data of our study. Pharmacokinetic trials in pediatric obesity should ideally include an in-depth analysis that allows for the study of the distinct influence of maturation versus overweight on drug pharmacokinetics 9as has been demonstrated for busulfan, midazolam, and metformin 1011 ,

Full size image. Vancomycin dosing in healthy-weight, overweight, and obese pediatric patients. Am J Health Syst Pharm. Sign In. As a separate approach to investigate the influence of body weight on vancomycin pharmacokinetics, we attempted to distinguish the influence of growth-related and obesity-related changes in weight.

This is substantiated by a pediatric pharmacokinetic study with vancomycin, where a body weight-dependent exponent was found to be superior compared to a simple model with TBW as a covariate, since this study was done in non-obese children mostly under 1 year of age Nederlands Kenniscentrum voor Farmacotherapie bij Kinderen. For each individual, AUC in boldC min at day 3, and AUC at day 1 are shown in the graph where color corresponds to the individual's renal function. Consequently, drug labels do not provide information on drug dosing in obese children, and specific guidelines for drug dosing in pediatric obesity are currently scant 7. Sherwin, and C.

Lastly, trough C min concentrations corresponding to the primary target were explored. The limited number of pharmacokinetic studies conducted has proposed different covariates for vancomycin clearance in obese children and adolescents. As for the use of weight in predicting clearance, it is important to realize that in pediatrics, weight can be a result of either growth reflecting age or excessive growth in obesity. Hagemann, Pharm.

Vancomycin serum drug concentrations were quantified using immunoassay via the Abbott Architect System. It has been shown for adults that obesity can impact drug pharmacokinetics by altering different physiological processes, such as cardiac output, renal and hepatic perfusion, and function of drug-metabolizing or transporting enzymes 45. Search SpringerLink Search. Annu Rev Pharmacol Toxicol.

Sign In. Annu Rev Pharmacol Toxicol. Sherwin, and C. As for the use of weight in predicting clearance, it is important to realize that in pediatrics, weight can be a result of either growth reflecting age or excessive growth in obesity. Br J Clin Pharmacol.

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  • Your comment will be reviewed and published at the journal's discretion. Data on demographics, lab values, and clinical PK data were extracted from the Intermountain Healthcare system enterprise data warehouse at the University of Utah between January 1,and December 31,

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Article Navigation. Vancomycin dosing in healthy-weight, overweight, and obese pediatric patients. It is unclear what explains these results, but it cannot be excluded that these findings are explained by the absence of adolescents with normal weight unlike the data of our study. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Smit, S. Hence, our data indicates that even though overweight or obese children might show some indication of hyperfiltration based on the Schwartz equation, this does not translate to an increased vancomycin clearance.

Drug disposition in obesity: toward evidence-based dosing. Pediatric obesity is typically defined using growth charts with vancomycin dosing in obesity in children and sex-specific values for the body mass index BMI. Expert Committee. Paediatric Formulary Committee. To evaluate existing dosing guidelines and, if necessary, design a new guideline, concentration-time profiles were simulated for several typical individuals from the dataset with different ages, body weight, and renal functions using the ranges found across the dataset. These principles presumably also apply to obese children, although well-designed studies that explore this are scarce 56.

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