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Table 1 Methods for drugs dosing applied to children with obesity

From: Drug dosing in children with obesity: a narrative updated review

Body Descriptor/ Equation/ Population

Remarks

TBW

TBW: drug dose *kg

Pediatric (up to 40 kg and 12 Years)

Not recommended for lipophilic drugs. For unfractionated heparins a lower dose is recommended [12].

BSA

BSA (m2) = square root of (height (cm) x weight (kg)/3600)

Children and adults

This method is used for both adults and children especially for dosing chemotherapy drugs.

IBW

IBW = [50th percentile weight (age)*height(cm)]

Age 2-20 years

Accurate determination of IBW is important for the proper dosing of medications, such as acyclovir, digoxin, and morphine. There is no consensus on the most accurate calculation in children. The growth chart-based Moore’s method determines IBW by looking at the same weight percentile line as the child’s height percentile for that age.

BMI

BMI chart for age (weight in kilograms divided by the

square of height in meters).

Age 2–20 years

A high BMI can be an indicator of high body fatness. Pediatric BMI should be correlated with growth curves and percentiles.

Allometric scale

Dose in children = adult dose * (TBW of a child/70)0.75

Age 2–20 years

Drug dose is predicted using allometry, depending on the properties of the drug such as free fraction in adults, pharmacodynamics and binding proteins [13].

Fat Free Mass

FFM = weight [kg] * [1 - (body fat [%]/ 100)]

Adults

Fat-Free Mass (FFM) refers to all body components except fat. It includes water, bone, organs and muscle content with different measure for males and females.

Age scaling

The dose is selected according to the child’s age using charts.

Over six months age.

This method does not take into account the changes due to developmental growth that occurs within each age group (e.g., the hepatic metabolic capacity of an infant child is different from that of a neonate)

Physiologically Based Dosing

Based on pathophysiology and changes in obesity, drug binding or distribution volume. The adipose tissue succeeds in getting the lipophilic molecules, making them less available for therapeutic effect. The increase in the blood volume and cardiac output of the child affected by obesity and the alteration of plasma proteins create alterations in the distribution of drugs [13, 14]

Clearance Based Scaling

• Dose for the child = adult dose *(CL in the child/CL in adults)

• CL in the child = CL in adults * (TBW of a child/70) exp

The fixed exponent of 0.75 is commonly used and predicts reasonably well for children older than 2 years of age (as used generally in allometric scaling) [15].

A. Clearance is a measure of the drug metabolism in the gut and liver and/or their renal elimination.

B. Obesity is a predisposing factor for liver steatosis in both adults and children, involving reactions that require modification and therefore the elimination of drugs. CYP3A4 activity is reduced in obese patients.

The Clearance based method takes into account renal function too in terms of

Volume of distribution and clearance. Obesity can affect kidney enzyme functions

  1. Adapted in part from Xiong Y, Fukuda T, Knibbe CAJ, Vinks AA. Drug Dosing in Obese Children: Challenges and Evidence-Based Strategies. Pediatr Clin North Am. 2017;64(6):1417–38 [16]
  2. BSA Body Surface Area, CL Clearance, FFM Fat Free Mass, IBW Ideal Body Weight, TBW Total body weight