How Should Medications Be Dosed in Obese Children?
There is little evidence in the literature supporting the use of adjusted body weights to calculate safe and efficacious doses in obese children. Using standard methods to calculate doses assumes that body composition and function are similar in obese and nonobese children. This assumption may not be true because the excess weight in obese children does not consist of adipose tissue and lean body mass in the same proportion as in nonobese children. It is important to realize that total body weight (TBW) for dose calculations could lead to supratherapeutic doses, whereas using ideal body weight (IBW) could result in subtherapeutic doses.
There are currently few data in the literature evaluating the impact of obesity on the pharmacokinetics of medications commonly used in the pediatric population. Some pharmacokinetic dosing considerations are discussed below.
Loading dose. Although the evidence in the literature to support a particular approach to calculating loading doses in obese children is controversial, data are sufficient to suggest that hydrophilic drugs with a small volume of distribution in normal-weight patients, such as aminoglycosides, should have loading doses calculated using IBW or a percentage in excess of IBW instead of TBW.
The distribution of highly lipophilic medications, on the other hand, is not as predictable because the volume of distribution may not be larger in obese patients and the lipophilic medication may not distribute into adipose tissue extensively, as expected. For lipophilic medications that are primarily distributed into fat tissue or are freely distributed between lean and fat tissue, loading doses should be based on TBW. An alternative to administering a single large loading dose based on TBW is to split the loading dose into smaller doses and administer multiple mini-loading doses, with assessment of patient response after each dose.
Maintenance dosing. Clearance, which is based on metabolism and organ perfusion, is important when determining a maintenance dose. Because lean mass in obese children represents a smaller proportion of excess weight, clearance of medications does not increase proportionally with weight.
One approach for determining maintenance doses in obese children is to use a calculation based on lean mass (eg, lean body weight). However, this approach can be problematic because there is currently no straightforward way to calculate a child's lean body weight, and data from the limited studies evaluating this pharmacokinetic approach are inconclusive. Therefore, alternative approaches that do not solely consider overall body size still need to be developed so that accurate maintenance doses can be determined for obese children.
For effective and safe medication use, the PPAG recommends consideration of pharmacokinetic analysis whenever possible for adjusting medications in overweight or obese children.
More research is urgently needed to determine the effect of obesity on drug dosing and safety. To that end, the Pediatric Trials Network is developing a drug database with dosing guidelines for obese children that will help identify major gaps in this knowledge.
Dosing in Obese Children
There is little evidence in the literature supporting the use of adjusted body weights to calculate safe and efficacious doses in obese children. Using standard methods to calculate doses assumes that body composition and function are similar in obese and nonobese children. This assumption may not be true because the excess weight in obese children does not consist of adipose tissue and lean body mass in the same proportion as in nonobese children. It is important to realize that total body weight (TBW) for dose calculations could lead to supratherapeutic doses, whereas using ideal body weight (IBW) could result in subtherapeutic doses.
Dose Calculations Using Pharmacokinetics
There are currently few data in the literature evaluating the impact of obesity on the pharmacokinetics of medications commonly used in the pediatric population. Some pharmacokinetic dosing considerations are discussed below.
Loading dose. Although the evidence in the literature to support a particular approach to calculating loading doses in obese children is controversial, data are sufficient to suggest that hydrophilic drugs with a small volume of distribution in normal-weight patients, such as aminoglycosides, should have loading doses calculated using IBW or a percentage in excess of IBW instead of TBW.
The distribution of highly lipophilic medications, on the other hand, is not as predictable because the volume of distribution may not be larger in obese patients and the lipophilic medication may not distribute into adipose tissue extensively, as expected. For lipophilic medications that are primarily distributed into fat tissue or are freely distributed between lean and fat tissue, loading doses should be based on TBW. An alternative to administering a single large loading dose based on TBW is to split the loading dose into smaller doses and administer multiple mini-loading doses, with assessment of patient response after each dose.
Maintenance dosing. Clearance, which is based on metabolism and organ perfusion, is important when determining a maintenance dose. Because lean mass in obese children represents a smaller proportion of excess weight, clearance of medications does not increase proportionally with weight.
One approach for determining maintenance doses in obese children is to use a calculation based on lean mass (eg, lean body weight). However, this approach can be problematic because there is currently no straightforward way to calculate a child's lean body weight, and data from the limited studies evaluating this pharmacokinetic approach are inconclusive. Therefore, alternative approaches that do not solely consider overall body size still need to be developed so that accurate maintenance doses can be determined for obese children.
Drug Levels
For effective and safe medication use, the PPAG recommends consideration of pharmacokinetic analysis whenever possible for adjusting medications in overweight or obese children.
Conclusion
More research is urgently needed to determine the effect of obesity on drug dosing and safety. To that end, the Pediatric Trials Network is developing a drug database with dosing guidelines for obese children that will help identify major gaps in this knowledge.
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