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

Abstract

Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight‐based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment.

Drug dosing in children with obesity: a narrative updated review

“…Modifications in these PK parameters as well as other obesity-related alterations, including those in drug absorption and metabolism, might affect the drug therapeutic index, that is a ratio comparing the blood concentrations at which a specific drug exerts its therapeutic effect to those associated to occurrence of toxicity [5,6]. Moreover, in children and adolescents with obesity the effect of gender on drug absorption and metabolism are rarely considered in spite of gender differences in obesity-related metabolic syndrome clustering before and after puberty [7], and sex related differences in gastrointestinal physiology and intestinal microbiome [8].…”

“…In June 2020, Ameer et al [5] published a comprehensive review of the drugs most widely used for the treatment of diseases in infants, children, and adolescents with obesity. The reviewed literature, covering the period from 1970 to 2018, focused on drugs used in hospital and highlights that the enrolled cohorts are often small, and large variability on methods was used for drug dosing.…”

“…The reviewed literature, covering the period from 1970 to 2018, focused on drugs used in hospital and highlights that the enrolled cohorts are often small, and large variability on methods was used for drug dosing. To provide an update and an extension of Ameer's data [5], here we reviewed the existing recommendations and suggested methodological approaches for drug dosing in children with obesity considering drugs commonly prescribed both in-and out-of-hospital settings.…”

Filling the Gap in Knowledge for Drug Dose Individualization in Pediatric Obesity

“…In a literature review published in this issue of Obesity , Ameer and Weintraub (2) review 4 decades of pediatric PK and PD literature focused on 70 frequently prescribed drugs in the pediatric inpatient setting. The focus on commonly prescribed drugs is important for judicious clinical practice, drug efficacy, and safety.…”

“…Overall, the literature review by Ameer and Weintraub (2) provides an excellent overview and critique of the currently available data to support evidence‐based drug dosing for children with obesity. Continued research (both retrospective and prospective) is imperative to improve our knowledge base in this arena.…”