Article Text

  1. J N Van Den Anker1
  1. 1Pediatrics, Children's National Medical Center, Washington, DC, USA


Objective Well-known differences exist in the disposition of and response to medicines between children and adults and between infants and children of different ages. Yet, as well-designed clinical studies in children are scarce, dosing schemes are usually derived in an empirical manner from clinical trials in healthy volunteers and/or restricted adult patient groups. Instead of an empiric dosing regimen based on body weight alone, paediatric dosing regimens should be based on an understanding of the developmental aspects of pharmacokinetics, pharmacodynamics and pharmacogenomics of the studied medicine in children. In addition the impact of disease, environmental influences and drug interactions need to be investigated.

Methods Pharmacokinetic and pharmacodynamic parameters of some pain medications are simultaneously estimated in young infants. Following the characterisation of the variability in pharmacokinetics and pharmacodynamics all other sources of intra and interindividual variability are investigated. For example, the role of pharmacogenomics on pharmacokinetics and pharmacodynamics of morphine will be demonstrated.

Results Variability in genes encoding the enzyme metabolising morphine (eg, the UGT2B7 gene), opioid receptors and blood–brain barrier transport of morphine by multidrug resistance transporters influence the clinical efficacy of morphine, showing that genetic variability in non-opioid systems may also directly influence the clinical efficacy of opioids.

Conclusions Genotype-specific dosing regimens have the potential to be more precise and more prudent. However, not all variations in drug responses are related to pharmacogenomic variations. Drug response can be modulated by a number of non-genetic factors, especially co-medications, the presence of concurrent disease or the developmental stage of the exposed individual.

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