A–Z of prescribing for children

E – Excretion

Excretion is the final phase of the drug's journey as it passes through the body, and this elimination – usually by the kidneys – depends on glomerular filtration, tubular excretion and also tubular reabsorption (Van den Anker et al, 2018). However, the processes are clearly influenced by nephrogenesis – or the kidney's development – in an infant (Sage et al, 2014).

Normal nephrogenesis begins at 9 weeks' gestation and is complete by 36 weeks' gestation, which is then followed by postnatal changes in the blood flow in the kidney (Kearns et al, 2003). Therefore, premature and low birthweight babies will have under-developed kidneys: lower birthweight babies will have fewer glomeruli per unit area in the cortex than normal birthweight babies (Manalich et al, 2000). Nevertheless, term babies' kidneys will be nephrogenetically complete, as there are no more nephrons formed after 36 weeks' gestation (Bertram et al, 2011). However, the kidney still does not reach full maturity until the child reaches puberty (Eidelman and Abdel-Rahman, 2016), and structural differences are well described between neonate and adult kidneys (Box 1).

Box 1.Comparison of neonate to adult kidney(Eidelman and Abdel-Rahman, 2016)

Due to these structural differences, the capacity for a newborn to eliminate drugs is reduced, so younger children and infants often require drug dosing less frequently for renally cleared medications (Eidelman and Abdel-Rahman, 2016). There is immature glomerular filtration and tubular function in younger children (Hill et al, 2022). Glomerular filtration is where a large quantity of water-soluble drugs and drug metabolites are eliminated, and the glomerular filtration rate (GFR) is often used to assess renal function (Van den Anker et al, 2018).

The GFR is approximately 10–20 mL/min/m² at birth (Lu and Rosenbaum, 2014) and increases to 20–30 mL/min/m² during the first few weeks of life, and then reaching half of the normal adult values by 3 months of age (O'Hara et al, 2015); adult levels are reached by around age 2 years (O'Hara, 2016). Drug doses will therefore need to be adjusted frequently during the first few weeks and months of life, either by increasing the dosing interval, or reducing the dose (Van den Anker et al, 2018).

Creatinine clearance is often used to estimate GFR (Schwartz et al, 2009). Creatinine is a type of chemical compound that is left over from specific energy producing processes in the muscles. From the age of 1 month, serum creatinine levels gradually increase due to the child's increase in body size and muscle mass (Chuang et al, 2021), so knowledge of GFR predictions and creatinine clearance levels at different ages is essential (Pierrat et al, 2003).

Conversely, tubular secretion and reabsorption capacity mature at much slower rates than glomerular filtration, with tubular reabsorption not reaching adult levels until around two years of age (Lu and Rosenbaum, 2014), which will evidently have an impact on particular drug clearance rates. It is clear that immature kidneys will result in inefficient elimination of some drugs, thus increasing the half life.

The pH of the urine can also affect the reabsorption of any weak acids or bases, which can then consequently affect the elimination. The urine pH in adults is higher than in infants, so this will affect the reabsorption of weakly acidic drugs (Batchelor and Marriott, 2015).

Developmental changes in the kidney can have an impact on GFR and estimating GFR in neonates and young children remains a challenge (Van den Anker et al, 2018). Age, weight and body surface area all need to be considered, alongside the potential of genetic differences, and all can contribute to a variability in pharmacokinetics: understanding this culmination can enhance the understanding of dosing of medications for neonates, infants and young children (Barker et al, 2018).

The next article in the series will focus on F – Formulations.