Drug Dosing and Pharmacokinetics in Children With Obesity

A sixth of children in the United States are affected by obesity. When a person is obese, their body composition and physiology is altered, which results in a change in effects associated with drug dosing and pharmacokinetics. Thus, the effect of  drug disposition on obesity can possibly lead to therapeutic failure or toxic side effects. Although this fact is well known, there is little information known about the effect of childhood obesity of drug pharmacokinetics. Currently, there is no comprehensive, evidence based understanding of the effect of childhood obesity of drug pharmacokinetics. Thus, researchers conducted a systematic review to find studies in the last 40 years that provided evidence of the effect of obesity on drug disposition in children. They searched literature databases to find if any studies contained data on drug clearance, volume of distribution, or drug concentration in obese children.

Researchers were able to discover 20 studies in the last 40 years that met the inclusion criteria and contained pharmacokinetic data for 21 drugs. Out of these studies, 11 out of 17 drugs had clinically significant pharmacokinetic alterations observed in children with obesity. In addition, for 5 out of 13 drugs studies showed that pharmacokinetic alterations resulted in substantial differences in exposure between children with and without obesity. Overall, studies indicated important obesity-related changes in drug pharmacokinetics. However, there were many limitations associated with these studies. For example, the majority of studies included small numbers of children. Furthermore, many drugs that were studies are not commonly prescribed drugs. There was no data for several important drug classes where obesity-related toxic overdosing or subtherapeutic underdosing may have been previously observed in adults, such as in acute care, cardiovascular, and anesthesia.

After reviewing these articles, researchers concluded that the relative information available about the drug pharmacokinetics of children who are obese is concerning, because it is so limited. To account for physiological and pharmacologic factors, some physicians adjust weight-based dosing using various metrics of body size, such as ideal body weight. However, this dosing strategy is largely based on theory or extrapolated data from studies in adults. Some analyses have identified that these dosing strategies may give false predictions of clearance and other pharmacokinetic values. To address this issue, researchers are currently collaborating with the National Institute of Child Health and Human Development in a systematic review of acute care and commonly used drugs to develop a pharmacokinetic database for obese children. As a result, data generated from this review will be utilized to make appropriate dosing recommendations for obese children. For future studies about pharmacokinetics in obese children, researchers hope to focus on including drugs if different therapeutic drug classes, based on drug use, medical need, and expected pharmacokinetic alterations in obesity (based on adult studies).

After reviewing this article, I was surprised to find that there were very few studies published about the pharmacokinetic factors of drugs in obese children. Since there are many children who are obese in the United States, I believe it is important to discover the pharmacokinetic parameters of drugs in obese children. With more information available, pharmacists and physicians will be able to better treat these children. Did you find this article surprising? Why or why not? Do you have any thoughts on why there have not been many studies published about childhood obesity and drug pharmacokinetics?

 

Harskamp-van Ginkel MW, Hill KD, Becker KC, et al. Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review. JAMA Pediatr. 2015;169(7):678-685.