Physiology and PK differences with age

It has long been recognised in medicine that neonates and children cannot simply be considered small adults. Increasing evidence also suggests that older and frail patients should be considered pharmacokinetically and pharmacodynamically different from adults.

Physiological changes occur over an individual’s lifetime that affect the distribution and clearance of aminoglycosides, affecting the pharmacokinetics and recommended dosing regimens.

Of most importance are:

• Body water content and distribution: Newly born babies have a significantly greater proportion of total body water and a greater amount resides outside of the cells, when compared to adults. In older age, the total amount of body water decreases as musculature and body mass decline. As we explained back in week 2, this results in a larger volume of distribution (Vd) in neonates, which reduces in adulthood and through older age. But in addition to this are changes in renal function.
• Renal function: The kidneys are not fully developed early in life. However, glomerular filtration, thus aminoglycoside clearance, rapidly increases in early life and reaches adult levels by 6 months of age. Renal function, overall, reaches a maximum in adolescence and then gradually declines through adult and older age. Therefore, aminoglycoside clearance will also decline gradually through adulthood in line with renal function.

Take a look at the image below, which is a timeline depicting the changes in body water distribution and renal functions with age.

If you require a screen reader-compatible version this is available as a PDF.

Both of these factors are important to consider when using aminoglycosides in a young or elderly patient. In the next step, we will examine clinical strategies for neonates and children.