Relationship Between Drugs and Functional Activity of Various Mammalian P-Glycoproteins (ABCB1)

Suresh   V.   Ambudkar; In-Wha      Kim; Catherine      Booth-Genthe

Abstract

P-glycoprotein (Pgp, ABCB1) is an efflux transporter for a variety of amphipathic agents that can affect the pharmacokinetics of drugs. In order to extrapolate transport and pharmacokinetic data of the drug candidates obtained from in vitro and animal models to those in humans, it is important to understand the functional differences of Pgps from various mammalian species including human, monkey, dog, rat, and mouse. Here, we review differences/similarities in the properties of Pgp from numerous mammalian species commonly used in preclinical studies and discuss their relevance to the pharmacokinetics of potential drug molecules.

Keywords: ABC transporter, ATP hydrolysis, chemoprevention, multidrug resistance, pharmacokinetics, species differences, structure-activity relationship