Pharmacokinetics of Antimicrobials in Obese Children
Mr Sampson1, M Cohen-Wolkowiez2, Dk Benjamin2
1Duke Clinical Research Institute, Durham, NC, USA ; UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Insights
Childhood obesity impacts antibiotic effectiveness due to altered pharmacokinetics. More research is urgently needed to ensure safe and effective antibiotic dosing in obese children, preventing treatment failures and toxicity.
Area of Science:
- Pediatric Pharmacology
- Pharmacokinetics
- Obesity Medicine
Background:
- Childhood obesity is a growing concern associated with significant health issues.
- Antibiotics are frequently prescribed for obese children.
- Physiological changes in obese children can alter drug pharmacokinetics, complicating dosing.
Purpose of the Study:
- To review existing pharmacokinetic data for antibiotics in obese children.
- To highlight the implications of these findings for drug dosing strategies.
- To identify knowledge gaps in antibiotic pharmacokinetics for this population.
Main Methods:
- A comprehensive literature search was performed across PubMed, EMBASE, and International Pharmaceutical Abstracts.
- Search terms included obesity, pharmacokinetics, drug toxicity, dosing, and various antimicrobial classes.
- Studies specifically investigating antibiotic pharmacokinetics in obese children were included.
Main Results:
- Four pharmacokinetic studies of antibiotics in obese children were identified (cefazolin, tobramycin, gentamicin, vancomycin).
- Only one study was prospective; two studies reported pharmacokinetic differences necessitating dosing adjustments for tobramycin and gentamicin.
- Significant variability exists in drug distribution characteristics among the studied antibiotics.
Conclusions:
- There is a pronounced lack of pharmacokinetic studies for antibiotics in obese children.
- The scarcity of data hinders accurate drug disposition prediction and rational dosing strategies.
- Urgent research is needed to establish appropriate dosing guidelines, addressing a critical public health concern.
Introduction:
Childhood obesity is common and results in substantial morbidity. The most commonly prescribed drugs in obese children are antibiotics. However, physiologic changes associated with childhood obesity can alter antibiotic pharmacokinetics and optimal body size measures to guide dosing in his population are ill defined. This combination can result in therapeutic failures or drug-related toxicities. This review summarizes pharmacokinetic information for antibiotics in obese children and implications for dosing.
Methods:
We conducted a comprehensive literature search of PubMed, EMBASE, and International Pharmaceutical Abstracts to identify pharmacokinetic studies of antimicrobial agents in obese children. We included the following search terms: obesity, pharmacokinetics, pharmacodynamics, drug toxicity, dosing, anti-infective agents, antiviral agents, and antifungal agents.
Results:
We identified four pharmacokinetic studies of antibiotics in obese children: one for cefazolin and tobramycin, one for gentamicin, and two for vancomycin. Only the cefazolin/tobramycin trial was prospective. The drugs studied differ in their tissue and body water distribution characteristics. Two of the studies (tobramycin and gentamicin) reported pharmacokinetic differences and required dosing modifications in obese children.
Discussion:
The lack of pharmacokinetic studies in obese children is pronounced. The scarcity of pharmacokinetic data limits the ability to predict drug disposition using drug physicochemical properties and impedes a rational approach to selection of appropriate body size measures for dosing. Given this knowledge gap, additional trials in obese children are urgently needed and is a public health concern.
Conclusion:
Pharmacokinetic studies of antimicrobials in obese children are desperately needed to guide dosing and avoid therapeutic failures or unwanted toxicities.
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