Clinicians Should Consider How Obesity Affects Pharmacokinetics in Children

In addition to the usual considerations of treating pediatric patients, clinicians should consider how pharmacokinetics may differ for children with obesity, according to a session at the 2021 virtual National Association of Pediatric Nurse Practitioners meeting.

The CDC defines obesity in children as weight at the ninety-fifth percentile or above, according to presenter Heather Herrera, RN, MSN, CPNP-AC/PC. For children between 2 and 19 years of age, this amounts to 18.5% or approximately 13.7 million obese children and adolescents. Furthermore, Herrera said is it estimated that approximately 20% of admissions to children’s hospitals involve children with obesity.

Obesity in pediatric populations has both long- and short-term implications and affects every single body system, Herrera said. Psychosocial impacts can include low self-esteem, depression, and eating disorders. Cardiovascular impacts can include dyslipidemia, hypertension, chronic inflammation, and endothelial dysfunction, while endocrine impacts include type 2 diabetes and precocious puberty.

Obesity in children also causes changes in physiology, such as changes in tissue composition, larger amounts of both fat body mass and lean body mass, and impaired liver and kidney function. Herrera noted that obese adults have shown increased blood volume, cardiac output, and renal blood flow.

When considering pharmacokinetics, Herrera said understanding volume of distribution (Vd) and clearance is essential. Vd is a theoretical parameter correlated to the total amount of drug distributed in the body and the resulting plasma level, which then determines the loading dose. It is the outcome measure most affected by obesity and it is determined mostly by the physiochemical properties of the drug and is specific to each individual, although it may vary in physiological and pathological conditions.

There are several body measurements to be considered, and each has its own uses and situations in which it is the most helpful. Ideal body weight (IBW) is a weight believed to be maximally healthful, based chiefly on height but modified by factors such as gender, age, and build. Total body weight (TBW) is a measure of mass in kilograms or pounds, whereas lean body weight (LBW) is the amount of weight that isn’t fat. Finally, adjusted body weight reflects lean body mass plus excess fat mass determined by a cofactor, and is a measurement mostly used in adults.

Notably, despite these options, Herrera said there is no gold standard for how to calculate IBW in children. For children taller than 5 feet, Herrera recommended the calculation (2.27 x [height in inches -60]) plus 42 for girls and plus 39 for boys. For children shorter than 5 feet, the formula is ([height in inches]2 x 1.65/1000).

When considering pharmacological challenges, it is important to identify correct dose of medication at the onset of therapy, particularly in critically ill children who need quick improvement. Notably, inadequate dosing can lead to treatment failure and adverse events.

In obese children, Herrera said volume of distribution and clearance are best represented by TBW and LBW, and these measurements are often used to determine dosage of a medication. The degree of lipophilicity and hydrophilicity should also be considered, as well as differences in loading versus maintenance dosing. Loading doses of hydrophilic medications in obese children should be based on IBW, whereas partially hydrophilic and lipophilic medications should be based on TBW.

Finally, Herrera reviewed common medication classes and various considerations in children with obesity. Obese children seem to require less heparin, enoxaparin, and warfarin per kilogram TBW than non-obese children, and may also require less vancomycin and aminoglycosides per kilogram.

By carefully considering pharmacokinetics and physiologic changes in children with obesity, clinicians can prescribe proper dosages and treatments for children, whether in mild conditions such as allergies or in more critical care cases.

REFERENCE

Herrera H, and Joiner J. Bigger is not always better: Pediatric obesity and its implications for critical care with case study discussions. NAPNAP 2021; March 27, 2021. https://napnap21.org/community/#/session-stream/42198. Accessed April 1, 2021.