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Carlijn Lems - Different dosage of medicines for children

Why is it that older children are better able to break down the blood pressure drug Viagra? Bachelor’s student Carlijn Lems used a computer model to find out. Doctors can use the results of her research to adjust the dosages of particular medicines so they are more appropriate for their young patients. Carlijn has been nominated for the Young Star Award 2020 on behalf of the Biopharmaceutical Sciences programme.

Varied study programme

‘I didn’t want to become a doctor, but I was interested in medicines and the human body,’ Carlijn explains. Because biology, maths and chemistry were also her favourite subjects, the bachelor’s programme in Biopharmaceutical Sciences was an easy choice for her. Carlijn: ‘It’s a very varied study programme. You learn about all the stages in the development path of medicines: from finding a medicine target in the body to clinical trials, but you also study the anatomy of the human body.’ During her studies, Carlijn learned that her passion did not lie in the lab, but in the computer: computational research was what really fascinated her. In this field, pharmacologists use computer models to predict how the body and medicines will interact. 

Drug breakdown

For her graduation assignment Carlijn made an in-depth study of the dosage of medicines for children. Children’s bodies are different from those of adults, and they therefore need a different amount of a drug. However, little is known about exactly how much of a drug is safe and effective. ‘One way of studying this is through clinical research,’ Carlijn says. ‘But it takes a lot of time and money to do that for each medicine and each age group. That’s why another solution is needed, and that’s where my research comes in.’
 
Children with too high blood pressure in their lungs are often prescribed the medication Sildenafil, better known as Viagra. Enzymes from the CYP3A family (CYPs) are responsible for breaking down this drug in the liver. Carlijn: ‘The amount of Sildenafil a child needs depends on how quickly the body breaks down the drug. And that depends on all kinds of bodily changes during the child’s development.’ Leiden researchers recently discovered that the rate of breakdown of the drug in children from the age of one to seventeen increases with age, although it isn’t yet known how this comes about. Carlijn therefore investigated which bodily changes could explain this increase.

Safe and effective

Carlijn used a computer model that combines the characteristics of the drug with those of the body, which allowed her to predict the rate of breakdown of the medicine at each age. ‘I also discovered two important causes of the increase in the rate of breakdown of the drug: the growth of the liver and the increase in the flow of blood through the liver.

‘We’ll be able to make medicines safer and more effective.’

Carlijn’s model was not able to fully explain the increase in the rate of breakdown. ‘That probably means that our knowledge of children's physical development is partially incorrect,’ she explains. ‘We already know that the working of the CYP enzyme and the amount of proteins in the liver are related to age, but my results show that there is a good chance that the image we currently have of how exactly these processes change may be wrong.’

In any event, Carlijn believes more research is needed. ‘That will help us to adjust the dosage as precisely as possible to children at any age. The same also applies to other medicines that are broken down by the same enzyme. We’ll be able to make medicines safer and more effective.’

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