Method development for quantification of DMET-proteins in the paediatric intestinal tract via LC-MS/MS using a QconCAT technique

Physiologically based pharmacokinetic (PBPK) modelling is a powerful alternative for paediatric clinical trials. Paediatric PBPK models require data on intestinal drug metabolising enzymes and transporter (DMET)-protein abundances, however only limited data is available. This is the first study to r...

Full description

Bibliographic Details
Main Authors: Jan Goelen, Richard D Horniblow, Hannah Batchelor
Format: Article
Language:English
Published: University of Huddersfield Press 2022-11-01
Series:British Journal of Pharmacy
Subjects:
Online Access:https://www.bjpharm.org.uk/article/id/1166/
Description
Summary:Physiologically based pharmacokinetic (PBPK) modelling is a powerful alternative for paediatric clinical trials. Paediatric PBPK models require data on intestinal drug metabolising enzymes and transporter (DMET)-protein abundances, however only limited data is available. This is the first study to report paediatric duodenal DMET protein quantification using a QconCAT approach. Thirty-six paediatric intestinal biopsies have been obtained from which the total mucosal protein was extracted. Proteins were digested to peptides using FASP and peptide levels were quantified using LC-MS/MS. Preliminary results provide some insight on the effect of age on duodenal protein abundance.
ISSN:2058-8356