P342 Mapping Transporter Interactions of Reference P-Glycoprotein Inhibitors

Márton Jani , Research & Development, SOLVO Biotechnology, Budaors, Hungary
Specific inhibition of P-gp is crucial in drug - transporter interaction studies, especially in assay systems based on primary or immortalized cells, or in in vivo studies. However transporter inhibition profile data are scarcely available on commonly used compounds that are considered P-gp specific.
The inhibitory interactions of P-gp inhibitors on a set of human drug transporters was undertaken in cellular uptake and vesicular transport settings. The panel of compounds was taken from the 2006 FDA Drug Interaction Draft Guidance.

Generally third generation inhibitors provided the lowest IC50s as well as highest selectivity. Notable cross reactions were observed on OATPs, BSEP as well as OCTs in the case of cationic inhibitors.