Custom-made pharmacology for seriously ill children
Medicines for adults are generally administered according to body weight. This approach is not suitable for premature babies, young children or people suffering from obesity. These patient groups require a more individually tailored approach. This was the theme of Catherijne Knibbes' inaugural lecture 'Predictable variation' on 3 December. Knibbe has been appointed Professor by Special Appointment in the Foundations of Individual Pharmacology.
Breakdown of medicines in the body
Catherijne Knibbe
Medicines and painkillers are distributed throughout the body once they have been administered, and are processed by the liver or the kidneys, and then excreted. The rate at which this process takes place is dependent on precisely what happens, in chemical terms, in the body. Knibbe's research among 250 premature babies - carried out in collaboration with Professor Dick Tibboel of the Sofia Kinderziekenhuis - showed that newborn babies younger than ten days old are much less able to break down morphine, irrespective of their body weight or the duration of the pregnancy. The body weight of the infants varied between 600g and 4 kg, and the duration of pregnancy from between 25 and 42 weeks. Older children, on the other hand, are able to degrade morphine faster than expected on the basis of the simple rule that the speed of the process is proportional to body weight. 'You can't treat a child of 10 kilo as one-seventh of an adult,' Knibbe summarises.
Personalised medicine
The research carried out by Knibbe and Tibboel was made by possible by special treatment procedures and advanced statistics which allowed the degradation of morphine to be followed closely using only between 1 and 4 blood samples per child, samples that were needed anyway for other purposes not related to the research. This resulted in a much improved model for determining the appropriate dosage of morphine, a step on the way to fully personalised medicine. Knibbe: 'Of course, you can always check the dosage afterwards in the bloodstream but you really want to know in advance, so that you get it right from the very first dose. We have since tested this model in ten children in Leuven and it went extremely well. There's very little that still needs to be changed.'
Over-protected children
It is not possible to carry out research on many other medicines and painkillers in children, which means that the prescribed dosage is still extrapolated from animal testing and clinical experience in adults. The problem is that clinical tests in children are only permitted by law if they benefit the sick child in question. For an initial test with a medicine, the practitioner is required to check first that a dosage is safe, without any therapeutic effect being expected. This is not permitted in children. Knibbe: 'Maybe in the Netherlands we tend to over-protect children, and there is too little opportunity to take into account the wishes of the children themselves, their altruistic motives. Children with a chronic illness tend to look at life differently. At times they can literally say: 'I know I am going to die, but I don't mind that injection if I know another child will benefit'.'