A–Z of prescribing for children

The third aspect of pharmacokinetics (after absorption and distribution) is metabolism. Most drugs are metabolised in the liver, but can also occur in the gastrointestinal tract, the blood, the kidneys, lungs and skin (Sage et al, 2014). The main purpose of metabolism is to decrease lipophilicity – when molecules are dissolving in fats, lipids or oils – in order to improve the renal clearance of the molecule (Lu and Rosenbaum, 2014).

Metabolic processes include specific chemical processes, including oxidation, hydrolysis, hydration, conjugation, condensation, reduction and isomerisation, with the end goal of making the drug easier to excrete (Hill et al, 2022). Such specific metabolic processes vary among different people, particularly neonates, children and adults.

Specific drug metabolism mechanisms are classified into Phase I and Phase II reactions, where Phase I reactions focus on altering the molecule of the drug, and the Phase II reactions focus more on conjugation with more water soluble aspects (Fernandez et al, 2011). With drugs that undergo Phase I metabolism, the enzymes of the Cytochrome P450 system are key, and include the gene families of CYP1, CYP2 and CYP3 (Skinner, 2008). These enzymes develop at different rates: some can be absent in neonates, developing by 4 months of age (e.g. CYP1A2), whereas some may develop rapidly in the postnatal period (e.g. CYP2A9) (Anderson, 2022). Such rates of developmental changes will ultimately determine the clearance rates of the drug, so it is vital – as a paediatric prescriber – to have a full comprehension of maturational profiles with regards to drug dosing (Jovanovic and Vucicevic, 2022).