ABC Transporters
It has been found that ABCB, ABCC, and ABCG families are all involved in the drug
transport. Because they are expressed in transporting epithelia, including the
intestine, liver, and kidney, they play a crucial role in the absorption, distribution, and
removal of drugs. Many of them are also related to mulitidrug resistance (MDR) of
tumor cells causing treatment failure in cancer. It has been well established that
active efflux by ABC transporters in the small intestine is a major contributor to poor
absorption and low bioavailability.
Three major ABC transporters, ABCB1/P-gp/, MRP1 and BCRP, have been showed to
localize to the apical/luminal membrane of enterocytes, and thus, are regarded to
form a barrier to intestinal absorption of substrate drugs. Generally, they are
expressed at high level in the brush border membrane of the intestine that can
effectively pump drugs back into the intestinal lumen to limit the extent of substrate
drug absorption. It is known that absorbed drugs must be transported from the site
of administration to the site of action. Therefore, the poor BBB (blood-brain-barrier)
permeability of the lipophilic drugs is due to the efflux functions of ABC transporters.
More recently, other ABC transporters, such as MRP2 and BCRP have also been
implicated in protecting the brain tissue against xenobiotics.
