How to administer medication safely in children

María Encarnación Blanco-Arana, a researcher at the UPV/EHU's Department of Analytical Chemistry, has studied the processes that a drug undergoes in the various body fluids and tissues when it is administered to children of different ages; the overall aim was to increase the information available with respect to the response of the child population to drugs. The results obtained in this study expand the information existing on the differences in the metabolism of the paediatric population and about the dosing of the drug Fentanyl –used as a substitute for morphine- in neonatology, thus constituting a step forward in safer, more effective administration.

One of the big problems currently facing clinical pharmacology is the scant information available on the dosing, effectiveness and safety of medication in the paediatric population. Mainly due to ethical and economic reasons, there is a lack of clinical trials that include children, and this means that there are not many drugs that have been officially prescribed for this population. In these cases, as Blanco explained, "the administering of the drug in the paediatric population is done on the basis of administering it in adults, in other words, by adjusting the dose on the basis of weight or body mass. However, this could constitute a dangerous practice as it is based on the hypothesis that children are miniature adults. This is not true because during the early stages of life, children's organs undergo a process of ongoing maturation and development, which means that the response of a newborn baby to a drug may not be the same as that of an older child or adult".

In order to increase the information available on how the child population responds to drugs, the UPV/EHU researcher used pharmacokinetic and metabolomic studies. In other words, she studied what the body does to the drug through the absorption, distribution, metabolism and elimination processes of the different paediatric age groups.

Drug behaviour in children

Part of the study was carried out on newborn piglets, as there are various studies that show that the metabolism of newborn piglets is very similar to that of newborn human babies.

Firstly, a pharmacokinetic study was made involving analysing blood samples from piglets given the drug Fentanyl. This drug is used as a substitute for morphine because in principal it is more powerful and is given in a smaller dose. The study covered different times, from the administering of it until it had been completely eliminated. For this purpose, "we used liquid chromatography coupled to a mass spectrometry detector (HPLC-MS) to develop an analytical method requiring small volumes of sample and which is capable of detecting low concentrations of the drug," explained Blanco. Thanks to this research, "we confirmed experimentally that the weight-based doses of this drug correspond to what happens in actual fact in the metabolism of the child population," she said. "The results obtained in this study expand the existing information on the dosing of this drug in neonatology, and constitute a step forward towards safer and more effective administration," added the researcher.

Secondly, metabolomics was used as a tool to study the differences between children of different ages and to observe the differences existing at each stage. "Through a plasma analysis and a multivariate analysis of the profile obtained, we managed to verify that it is possible to differentiate between pigs less than 5 days old and 8-week-old pigs. In the same way, we were able to see the differences in the urine of children under one year depending on their age. So the next step would be to detect the markers responsible for the differences relating to age and the degree of maturation, so they can be used to improve the dosing of drugs," pointed out Blanco.

As the researcher explained, "all these results are opening up the doors to new studies in which these compounds are analysed in a planned manner in order to improve the dosing of drugs in paediatrics".

Additional information

María Encarnación Blanco-Arana, graduate in Chemistry, wrote up her PhD thesis entitled Pharmacokinetics and metabolomics in paediatric studies at the Department of Analytical Chemistry of the UPV/EHU's Faculty of Science and Technology, under the supervision of Prof Rosa María Alonso-Rojas and the lecturer Oskar González-Mendia, both in the Department of Analytical Chemistry. The pharmacokinetic and metabolomics studies were conducted in collaboration with the Applied Pharmacokinetics and Pharmacodynamics group of the UPV/EHU's Faculty of Medicine, the Experimental Unit on Neonatal Physiology of University Hospital Cruces and the Istituto di Ricerca Pediatrica Città della Speranza of Padua (Italy).

Photos: Amanda Mills, USCDCP. Tere Ormazábal. UPV/EHU.