These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: P-glycoprotein protein expression versus functionality at the blood-brain barrier using immunohistochemistry, microdialysis and mathematical modeling.
    Author: De Lange ECM, Vd Berg DJ, Bellanti F, Voskuyl RA, Syvänen S.
    Journal: Eur J Pharm Sci; 2018 Nov 01; 124():61-70. PubMed ID: 30144528.
    Abstract:
    A proper understanding of P-gp mediated transport (functionality) at the blood-brain barrier (BBB) and beyond is needed to interpret, understand and predict pharmacokinetic (PK)- pharmacodynamic (PD) relationships of CNS drugs that are substrates of P-gp, especially since P-gp functionality may be different in different conditions. Often, P-gp expression is taken as a biomarker of transporter functionality. The aim of our study was to investigate whether brain capillary protein expression of P-gp is associated with changes in P-gp mediated drug efflux at the BBB. Status Epilepticus (SE) was induced by kainate in male rats. During 3-5 weeks post SE, hippocampal P-gp expression was determined using immunohistochemistry, while BBB P-gp functionality was assessed by microdialysis of quinidine, in absence and presence of the P-gp blocker tariquidar. The data were analyzed using Non-linear Mixed Effect Modeling implemented in NONMEM. Following SE, changes in brain capillary P-gp expression were observed. However, no relation between BBB P-gp protein expression and BBB P-gp mediated drug efflux was found. This warrants a critical view on the interpretation of reported changes in BBB P-gp expression as a biomarker of BBB P-gp functionality.
    [Abstract] [Full Text] [Related] [New Search]