P-glycoprotein efflux transporter activity often displays biphasic dose-response relationships

Abstract

The occurrence of P-glycoprotein efflux transporter systems is recognized as playing critical roles in chemotherapy, drug pharmacokinetics, and the bioavailability of environmental toxins. This article reveals that P-glycoprotein efflux transporter activity commonly displays a biphasic dose response, with low doses being stimulatory and high doses inhibiting. The quantitative features of these biphasic dose responses are consistent with the hormetic dose-response model and are independent of biological model and chemical class. These findings provide further support for the generalizability of the hormetic dose-response model while having important biological and clinical implications, including transport through the blood-brain barrier.