Study Models of Drug-Drug Interactions Involving P-Glycoprotein: The Potential Benefit of P-Glycoprotein Modulation at the Kidney and Intestinal Levels

• Type: Another Publication in an International Scientific Journal
• Date: 2023

Authors

Veiga-Matos, J (Author) Other; Morales, AI (Author) Other; Prieto, M (Author) Other; Fernando Remiao (Author) FFUP; Silva, R (Author) Other

Journal

Title: Molecules

Vol. 28 No. 3

Final page: 7532

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00Z-FE5

DOI: 10.3390/molecules28227532

Abstract (EN): P-glycoprotein (P-gp) is a crucial membrane transporter situated on the cell's apical surface, being responsible for eliminating xenobiotics and endobiotics. P-gp modulators are compounds that can directly or indirectly affect this protein, leading to changes in its expression and function. These modulators can act as inhibitors, inducers, or activators, potentially causing drug-drug interactions (DDIs). This comprehensive review explores diverse models and techniques used to assess drug-induced P-gp modulation. We cover several approaches, including in silico, in vitro, ex vivo, and in vivo methods, with their respective strengths and limitations. Additionally, we explore the therapeutic implications of DDIs involving P-gp, with a special focus on the renal and intestinal elimination of P-gp substrates. This involves enhancing the removal of toxic substances from proximal tubular epithelial cells into the urine or increasing the transport of compounds from enterocytes into the intestinal lumen, thereby facilitating their excretion in the feces. A better understanding of these interactions, and of the distinct techniques applied for their study, will be of utmost importance for optimizing drug therapy, consequently minimizing drug-induced adverse and toxic effects.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 46