Weight, age or body surface area? How paediatric doses are worked out
Children are not small adults, and dosing them by simple arithmetic from adult doses can go badly wrong. The science of getting it right starts with how the body matures.
In brief
Weight, body surface area or age? How paediatric doses are calculated, and why organ maturation in the first two years makes simple scaling unreliable.
- Weight-based dosing is the most common approach but fails at the extremes of age and size.
- Body surface area is standard for chemotherapy and some other narrow-margin drugs.
- Organ maturation, or ontogeny, matters most in the first two years of life.
Paediatric dosing looks like arithmetic and turns out to be physiology. Three approaches dominate, and each has blind spots.
Weight-based dosing
Most children’s doses are expressed in milligrams per kilogram. It is intuitive and easy to calculate at the bedside. But drug clearance does not rise in a straight line with weight. Scaling linearly from an adult dose tends to under-dose young children, who often clear drugs faster per kilogram, and can over-dose larger or heavier children unless a maximum is set.
Body surface area
For drugs with a narrow gap between effective and toxic doses, particularly chemotherapy, doses are often based on body surface area, calculated from height and weight. Surface area tracks some physiological processes more closely than weight does, though it adds a calculation step and a further source of error.
Age bands
Over-the-counter products and many fixed-dose formulations use age bands. They are simple for carers but crude, since children of the same age can differ greatly in size.
Why maturation matters most
The biggest differences between children and adults appear in the first two years of life. Enzymes that metabolise drugs, such as those in the cytochrome P450 family, mature at different rates. Some are barely active at birth and take months or years to reach adult capacity. Kidney function, measured by glomerular filtration rate, is low in newborns and rises quickly during infancy.
The result is that a newborn and a two-year-old of the same weight can handle a drug very differently. Modern paediatric dose-finding uses population pharmacokinetic models that combine size, often scaled allometrically, with a separate maturation function to capture this.
The special cases
Premature babies, children with obesity and children with kidney or liver disease each need their own considerations. They are also the groups least likely to have been included in the studies that set the label dose.
