Chapter 5: Special populations
Developmental pharmacology in neonates and children
Limited size, extensive variability
So, this chapter is it all about pharmacology in patients who are still developing.
Learning objective
This chapter highlights aspects of pharmacokinetics and pharmacodynamics (and safety) in children
and illustrate its relevance in clinical studies. The path goes from dose to concentration to effect. In
children, the key findings of the pharmacokinetics (absorption, distribution, metabolism and
elimination) will be different. This is due to transcutaneous absorption, a higher body water content,
a reduced metabolic capacity and a reduced elimination capacity. So, if you know everything in the
adult, you need to change the parameters in the child to give the medicine. If you give the same
dose, the child can develop seizures, heart rhythms, etc.. So, in developmental pharmacology, you
need to consider the change of the dose, but also the dose you want to reach in the body to really
treat the disease! The pharmacodynamics is all about the concentration to effect, about the
maturational differences. This is due to the neurotoxicity of ethanol, the hypothyroidism-related
cretinism, the neurotoxicity of hypoglycemia and the bilirubin toxicity (brain barrier). So, all the
pharmacokinetics and the pharmacodynamics parameters can change over time!
Limited size, extensive variability
“Pediatrics does not deal with miniature men and women, with reduced doses and the same class of
diseases in smaller bodies, but … It has its own independent range and horizon…”. A child is not (just)
a small adult! A newborn is not (just) a small child!
Developmental (dys)continuum throughout childhood
A newborn is the first four weeks of life. The infancy is the first years of life. When you are born, you
first lose some weight. Afterwards, the child will have 50% more weight. At the end of the first year
of life, it has tripled its weight. If you want to treat a child or an infant, the child will mature during
the treatment. So, the treatment needs to be depending on the maturing child. If we agree that the
pharmacokinetics part of the drug strongly relates to the metabolism of the organism, this is then
really an impressive change from a newborn to an adult! There are a lot of things changing in the first
years of life, especially in the metabolism.
In general, in common practice, drugs are developed for adults. That is what the market is for. Then,
we adapt the drugs in the needs of children. The majority of drugs are developed and focused on
adult diseases and adult formulations. We need to develop medicines to children and child diseases.
Developmental pharmacodynamics
All the explant cells used in this study are harvested through surgery, but the age of the cells is
different, the EC50 and the Emax is different. Researchers checked the calcium current in these cells. In
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