RLO: Clinical impact of changes in drug clearance

Age: Neonates

Total body clearance is reduced in neonates because of the immaturity of physiological processes in both the liver and the kidneys.

In the liver, the activity of both the cytochrome P450 enzyme system, required for phase I metabolism, and the conjugating enzyme systems required for phase II metabolism are reduced, and take several months to reach maturity. Drugs which rely on hepatic clearance can therefore accumulate in the body, leading to unwanted side effects and even toxicity. An example of this is "Gray Baby Syndrome" which results from the build up of the antibiotic chloramphenicol. Chloramphenicol is no longer used in neonates for this reason.

In terms of renal clearance, the rate of glomerular filtration is less than half that of adult values and tubular function is poorly developed in neonates. This means that drugs which rely heavily on renal clearance, such as the antibiotic gentamicin, can also build up in the system; serum concentrations should be determined to ensure appropriate dosing and avoid problems of toxicity.

 

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