Hochschulschrift:
Dissertation, Mathematisch-Naturwissenschaftliche Fakultät der Universität Greifswald, 2019
Anmerkungen:
Literaturverzeichnis: Seite 29-37
Text deutsch, Anhang englisch
Beschreibung:
In vitro, In vivo, Pharmakokinetik, Arzneimitteltransporter, Caco-2, Induktion
The efficacy and safety of pharmacotherapy is influenced by numerous pharmacokinetic processes. In addition to biotransformation processes mediated by CYP 450 enzymes, transport processes have become increasingly important. In these transport processes, drug transporters from the ABC and SLC families, which are located in the membranes of the enterocytes as well as in other organs, are involved. The expression and function of these drug transporters can be influenced for example by concomitantly administered drugs and thus, potentially result in drug-drug interactions. Several clinical drug-drug interaction studies have shown that underlying regulatory mechanisms are highly complex. In these studies, known inducers of drug metabolism and transport led to organ-specific alterations in pharmacokinetics of simultaneously administered drugs. The aim of this work was to contribute to a better understanding of expression and regulation of intestinal drug transporters and thereby to better predict alterations in pharmacokinetics. This included the contribution to the development and validation of a LC-MS/MS-based method for protein quantification. Using this method, the most strongly abundant membrane transporters ABCB1 (P-gp), ABCC2 (MRP2), ABCG2 (BCRP) and SLC15A1 (PEPT1) could be quantified even in very limited tissue samples. In parallel, the processes for mRNA isolation and quantification have been optimized. The Caco-2 cell model is widely used for the prediction of intestinal ...