Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

Abstract

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.

Systemic fluoroquinolone prescriptions for hospitalized children in Belgium, results of a multicenter retrospective drug utilization study

“…Overweight and obesity are increasingly prevalent among children, which creates specific dilemmas in drug dosing [ 35 ]. There were no specific recommendations available for FQ dosing for overweight and obese children in our centers, during the study period.…”

Inconsistencies in dosage practice in children with overweight or obesity: A retrospective cohort study

“…Although we found only one prescription had followed such a metric, individualized dosing by metrics of body size may be more feasible in overweight/obese children than common pediatric dosing strategies by TBW or fixed dose by age , . A reflection of the findings in this study, therefore, is that metrics of body size does not seem to be implemented in the clinic unless they have been “transformed” into clinical usefully guidelines.…”

“…Although we found only one prescription had followed such a metric, individualized dosing by metrics of body size may be more feasible in overweight/obese children than common pediatric dosing strategies by TBW or fixed dose by age. [5][6][7][8][9][10]16,17,19,20,23,[34][35][36][37][38][38][39][40][41][42][43][44][45][46] A reflection of the findings in this study, therefore, is that metrics of body size does not seem to be implemented in the clinic unless they have been "transformed" into clinical usefully guidelines. 48 In this study, we found that the capping dose was common practice, when the dose exceeded the maximum recommended adult dose.…”

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

“…We believe this approach to the question of the effect of obesity on drug dosing would identify medications likely to be relevant to general hospital practice. Prior pediatric reviews narrowed their coverage by focusing on one therapeutic category: for example, antimicrobials (86), area of practice (e.g., surgery (87) or emergency medicine (88)), or PK properties of drugs (14). The later major review yielded mostly uncommon drugs.…”