How significant is the role of P-glycoprotein in drug absorption and brain uptake?
Although P-glycoprotein (P-gp) is highly expressed in both intestinal epithelial cells and endothelial cells of brain capillaries, and functions as an efflux transporter in both organs, the impact of P-gp on intestinal absorption and brain uptake of drugs is quantitatively very different. The effect of P-gp on drug absorption is not quantitatively as important as suggested. Many drugs are good human P-gp substrates and yet exhibit reasonable oral bioavailability. In contrast, P-gp plays a quantitatively very important role in blocking the brain uptake of P-gp substrates. This review provides an overview of the role of P-gp in drug absorption and brain uptake, and explores possible factors that may explain the quantitative differences in the impact of P-gp on drug absorption and brain uptake.
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA. jiunn_lin@merck.com
Jiunn H
JH
Lin
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1