Lab Services - Contract Services


Ussing Chamber - Ussing Chamber Systems

Are you interested in transepithelial electrical measurements or in the assesmemt of intestinal permeability, or in other data? Your preferred choice would be using Ussing chamber systems for analysis.

Primacyt is offering in cooperation with the University Medicine of Greifswald, Department of Clinical Pharmacology Ussing chamber experiments with freshly excised intestinal tissue (jejunum, ileum, colon) from humans, pigs, and rats.

The vectorial transport of orally administrating substrates over the intestinal barrier is one of the critical determinants of bioavailability and efficacy of drugs. Therefore, the prediction of intestinal absorption is a crucial factor during early stages of drug discovery and development.

For transporter analysis of uptake and efflux transporters, some of the most used models are Caco2-cell monolayer cultures or other cell-based systems. Intestinal organoids are often used to determine the metabolism of substrates. However, none of the used models can combine all key determinants for the oral absorption of compounds, which are
  • Metabolizing enzymes including cytochrome P450 enzymes (CYPs) or uridine diphosphate glucuronosyltransferases (UGTs)
  • Drug efflux transporter proteins like P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) from the ATP-binding cassette transporter superfamily (ABC transporters) and;
  • Drug uptake transporter proteins such as the organic anion transporting polypeptides (OATPs), the organic cation transporters (OCTs) and the peptide transporter 1 (PepT1) from the solute carrier group (SLC).
Therefore, to get data more relevant for the in vivo situation, the US Food and Drug Administration (FDA) recommends using freshly excised human intestinal tissue mounted in the Ussing chamber, which provides both, a reasonable prediction of transporter interaction as well as intestinal metabolism.

The FDA has published Guidance for Industry 2015: Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System.


Literature
  • For a review of the used Ussing chamber model, please see Kisser et al., 2017.
  • Kisser B, Mangelsen E, Wingolf C, Partecke LI, Heidecke CD, Tannergren C, Oswald S, Keiser M: The Ussing Chamber Assay to Study Drug Metabolism and Transport in the Human Intestine. Curr Protoc Pharmacol, 2017, 77: 7.17.1-7.17.19. doi: 10.1002/cpph.22