Assistant: Apr. Lies De Bock

Pharmacokinetics and bio-analysis

The cytochrome P450 enzyme system plays an important role in the metabolism of many drugs. Previously published research in adults with liver cirrhosis showed significant alterations in the activity of most of the isoforms. The current project in our laboratory focuses on children with severe hepatic dysfunction. Liver tissue samples, taken from the sick liver from children undergoing liver transplantation, are investigated using several techniques. After isolating the microsomal fraction of the tissue, the enzyme activity of the six most important isoforms (CYP1A2, 2C19, 2C9, 2D6, 2E1 and 3A4) is determined with an incubation protocol, followed by the quantification of the specific metabolites using a UPLC-MS/MS method. The different CYPs are quantified using ELISA, and all patients are screened for genetic polymorphisms causing alterations in enzyme activity.

The combination of these data could be clinically relevant, as they could help identifying those drugs for which extra caution is necessary when used in children with liver disease. Additionally, the data are essential for the development of a Physiologically Based Pharmacokinetic model, used in the development of new drugs for this specific population.  

By Apr. Lies De Bock