Prospective Evaluation of the Dosing Regimen of Vancomycin in Children of Different Weight Categories

Nassar, Laila; Hadad, Salim; Gefen, Aharon; Shachor-Meyouhas, Yael; Mashiach, Tatiana; Krivoy, Norberto; Kassis, Imad

doi:10.2174/157488612805076606

Cited by 16 publications

(16 citation statements)

References 32 publications

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“…3–7 Consistent with previous studies, our study found that the weight-adjusted V d and CL decreased by 2.2% and 10.8%, respectively, in obese and overweight children compared with those with normal weight. One potential explanation for the small decrease in weight-adjusted V d is the hydrophilicity of and large size of vancomycin, which hinders drug distribution into adipose tissue.…”

Section: Discussionsupporting

confidence: 92%

“…One pediatric study found no statistical difference between different weight groups for weight-adjusted V d and CL. 3 In our study, we incorporated SCr, age, and ALWT for CL estimation.…”

Section: Discussionmentioning

confidence: 99%

“…4–7 Pediatric studies did not yield significant conclusions regarding differences in weight-adjusted V d and CL. 2,3,8,9 Notably, none of these pediatric PK studies used Bayesian analysis, which is better in predicting V d and CL in an obese population based on an understanding of the population PK properties and interindividual and intra-individual variability.…”

Section: Introductionmentioning

confidence: 99%

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Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

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Capparelli

Wahid

et al. 2015

Clinical Therapeutics

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Purpose The study objective was to compare different body size descriptors that best estimate vancomycin Vd and clearance (CL). Methods Patients between 3 months and 21 years old who received vancomycin for ≥48 hours from 2003 to 2011 were evaluated in this matched case-control study. Cases had body mass index in the ≥85th percentile; controls were nonobese individuals who were matched by age and baseline serum creatinine (SCr). Using a 1-compartment model with first-order kinetics, Bayesian post hoc individual Vd and CL were estimated. Findings Analysis included 87 matched pairs with 389 vancomycin serum concentrations. Median ages were 10.0 (interquartile range [IQR], 4.8–15.2) years for cases (overweight and obese children) and 10.2 (IQR, 4.5–14.8) years for controls (normal-weight children). Median weights were 44.0 (IQR, 23.4–78.1) kg for cases and 31.3 (IQR, 16.8–47.1) kg for controls. Mean (SD) for the baseline SCr values were also similar between the groups: 0.51 (0.22) (IQR, 0.34–0.67) mg/dL and 0.48 (0.20) (IQR, 0.30–0.60) mg/dL for the cases and controls, respectively. Actual weight and allometric weight (ie, weight0.75) were used in the final model to estimate Vd and CL, respectively. The mean Vd and CL, based on weight, for cases were lower than controls by 0.012 L/kg and 0.014 L/kg/h, respectively. Implications In obese children, actual weight and allometric weight are reasonable, convenient estimations of body fat to use for estimating vancomycin Vd and CL, respectively. However, these pharmacokinetic differences between obese children and those with normal weights are small and may not likely to be clinically relevant in dose variation.

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Section: Discussionsupporting

confidence: 92%

“…One pediatric study found no statistical difference between different weight groups for weight-adjusted V d and CL. 3 In our study, we incorporated SCr, age, and ALWT for CL estimation.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Lê

Capparelli

Wahid

et al. 2015

Clinical Therapeutics

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“…The remaining 20 publications contained PK data for 21 drugs, including 7 anti-neoplastic drugs, 4 anticonvulsants, 4 antibiotics, 3 analgesic/anesthetic drugs, 2 respiratory stimulants, and 1 immunosuppressant (Table 1). Six out of 21 (29%) drugs were not studied in a formal prospective PK trial (gentamicin 29 ; vancomycin 17,18,30 ; valproic acid 19 ; divalproex sodium 20 ; busulfan 21 ; and cyclosporine 36 ). PK data for these studies were collected following drug administration per standard of care, frequently with sparse sampling.…”

Section: Resultsmentioning

confidence: 99%

Drug Dosing and Pharmacokinetics in Children With Obesity

et al. 2015

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IMPORTANCE-Obesity affects nearly one sixth of U.S. children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxicity. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics (PK) and dosing in obese children is unknown.OBJECTIVE-To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children. EVIDENCE REVIEW-We searched the Medline, Cochrane, and Embase databases (January 1970-December 2012 and included studies if they contained clearance, volume of distribution, or drug concentration data in obese children (age ≤18 years). We compared exposure and weightnormalized volume of distribution and clearance between obese and non-obese children.

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“…Vancomycin is perhaps the most studied antimicrobial agent in obese children and adults . PK studies suggest a strong correlation between Vd and Cl with TBW in obese adults .…”

Section: Methodsmentioning

confidence: 99%

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

et al. 2017

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Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients.

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Prospective Evaluation of the Dosing Regimen of Vancomycin in Children of Different Weight Categories

Abstract: PK properties of all weight groups were similar. More frequent and higher doses are needed to achieve the goals of current guidelines.

Cited by 16 publications

References 32 publications

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Drug Dosing and Pharmacokinetics in Children With Obesity

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

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