Paediatric Drug Dosing and Pharmacokinetics
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Direct answer
Paediatric drug dosing and pharmacokinetics adjust adult doses for body size and for immature organ function, because neonates absorb, distribute, metabolise and excrete drugs differently. Body surface area is the preferred method for many agents, including several chemotherapy drugs, while weight-based dosing suits most others. Neonatal dosing must allow for low albumin, a larger share of free drug and immature hepatic and renal clearance.
What you must remember
- Mosteller formula: body surface area equals the square root of height in cm multiplied by weight in kg, divided by 3600, giving square metres.
- Clark's rule: child dose equals the adult dose multiplied by weight in kg and divided by 70, a rough estimate when height is unknown.
- Young's rule: child dose equals the adult dose multiplied by age divided by age plus 12, useful only for older children.
- Neonatal body water: a larger share of body water changes the volume of distribution, so loading doses are not simply scaled by weight.
- Neonatal protein binding: low albumin raises the free fraction of highly bound drugs and of bilirubin, increasing toxicity.
- Immature clearance: low glomerular filtration and immature glucuronidation prolong half-lives, so gentamicin needs longer dosing intervals in the first week.
- Avoid in neonates: chloramphenicol (grey baby syndrome), sulfonamides and ceftriaxone in hyperbilirubinaemia, and tetracyclines (teeth and bone effects).
A stepwise approach to a safe paediatric dose
Paediatric prescribing is a sequence of checks rather than one calculation. The steps below move from choosing the method to screening for toxicity, so that the dose is safe for the child's size and maturity.
- Choose the method: use mg/kg dosing for most drugs and body surface area for chemotherapy and some other agents, reserving age-based rules for when weight is unavailable.
- Calculate body surface area: apply the Mosteller formula, then multiply the dose per square metre by the calculated area.
- Use rules of thumb with care: Clark's rule and Young's rule give estimates that are less accurate than body surface area, and they should not replace it when precision matters.
- Adjust for neonatal physiology: allow for low albumin, immature liver enzymes and low glomerular filtration, which all lengthen drug half-lives and raise toxicity.
- Check the ceiling: cap the calculated dose at the adult maximum and confirm the concentration and volume a child can safely receive.
- Screen for contraindications: check age-specific warnings, especially for neonates, before the first dose is given.
Dosing errors in children usually come from a missed step in this sequence, rather than from arithmetic alone.
Where the exam tries to catch you
Pharmacokinetics questions reward knowing the mechanism behind an avoidance rule. Each trap below pairs a drug with a neonatal or paediatric risk.
- Trap: scaling an adult dose by age alone for a 3 kg neonate. Correct: neonates must be dosed by weight and maturity, because age-based rules do not capture immature clearance.
- Trap: choosing ceftriaxone freely in a jaundiced neonate. Correct: ceftriaxone displaces bilirubin and can precipitate with calcium, so it is avoided in hyperbilirubinaemic neonates, especially with calcium-containing infusions.
- Trap: treating chloramphenicol as a safe alternative in neonates. Correct: neonates lack adequate glucuronidation, so chloramphenicol accumulates and causes grey baby syndrome.
Frequently asked questions
What is the Mosteller formula for body surface area?
The Mosteller formula calculates body surface area as the square root of height in centimetres multiplied by weight in kilograms, divided by 3600, giving square metres. It is the commonest formula used for paediatric chemotherapy dosing. Doses are then expressed per square metre of body surface area.
Why do neonates need different dosing intervals from older children?
Neonates have low glomerular filtration and immature hepatic enzymes, so drugs such as gentamicin are cleared slowly. Dosing intervals are therefore lengthened in the first week of life. Their larger body water also alters the volume of distribution, so loading doses are not simply scaled by weight.
Why is chloramphenicol avoided in neonates?
Neonates lack adequate glucuronidation to conjugate chloramphenicol, so the drug accumulates in the plasma. This causes grey baby syndrome, with abdominal distension, vasomotor collapse and grey cyanosis. Chloramphenicol is therefore avoided in neonates unless no safer alternative exists.
Why is aspirin avoided in children with viral illness?
Aspirin is avoided in children with viral infections, especially chickenpox and influenza, because it is linked with Reye syndrome. Reye syndrome causes acute encephalopathy and fatty liver. Paracetamol or ibuprofen are the usual antipyretics in these children.
What is Clark's rule for paediatric dosing?
Clark's rule scales an adult dose by weight, multiplying the adult dose by the child's weight in kilograms and dividing by 70. It is a rough estimate that is useful when height is unknown. Body surface area is preferred where accuracy matters, such as in chemotherapy.