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P51 A combined experimental approach to assess intestinal drug absorption in early childhood

2019; BMJ; Volume: 104; Issue: 6 Linguagem: Inglês

10.1136/archdischild-2019-esdppp.89

1468-2044

Márton Kiss, Johan Nicolaï, JJMW van den Heuvel, Richard Mbasu, SM Botden, JB Koenderink, Frans G. M. Rüssel, AL Ungell, Saskia N. de Wildt,

Metabolism and Genetic Disorders

Background Drug transporters and metabolizing enzymes located in the epithelial lining of the intestine limit or enhance systemic drug exposure. During child development, the abundance and activity of these transporters and enzymes - determining how fast and how much of a drug is being absorbed into the circulation - changes from birth to adolescence. As most drugs given to children are taken by mouth, the aim of this project is to study the abundance and activity of transporters and metabolizing enzymes, involved in the intestinal absorption of drugs. Methods The ex vivo Ussing chamber with pediatric small intestinal tissue is applied to evaluate intestinal drug absorption and metabolism. 1 Transport and metabolism of a selection of drug molecules is assessed across these tissues by sampling the donor and receiver compartment at different intervals and sample analysis by LC-MS/MS. Viability, functionality and integrity of the tissues are monitored using electrophysiological parameters (dP, R, I). Ussing chamber experiments are combined with a targeted proteomics approach to quantify drug transporter and metabolizing enzyme abundance in these tissues. Results An Using chamber method has been successfully set up using both adult and pediatric intestinal tissue. To date samples from three children of different ages have been evaluated and show promising results. Tissue from the same patients has been stored for proteomics analysis. Conclusion The Ussing method presents an innovative, feasible approach to study active intestinal transport in children. Further studies are now underway to elucidate age-related variation in intestinal transport and metabolism. Reference Sjöberg Å, Lutz M, Tannergren C, Wingolf C, Borde A, Ungell AL:Comprehensive study on regional human intestinal permeability and prediction of fraction absorbed of drugs using the Ussing chamber technique. Eur J Pharm Sci 2013 Jan 23;48(1–2):166–80. Disclosure(s) The collaboration project is financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. Johan Nicolaï, Richard Mbasu and Anna-Lena Ungell are employees of UCB Biopharma SPRL.