ABSTRACT
The activity of transporters is now widely accepted as an important determinant of drug disposition. Certainly one major reason that transporters have become a key area of research that continues to grow involves the efflux pump, P-glycoprotein (P-gp). The transporter was initially discovered by Juliano and Ling as a transmembrane (TM) protein that was overexpressed in Chinese hamster ovary (CHO) cells treated with various chemotherapeutic agents that had become resistant to these cytotoxic drugs. P-gp was initially discovered by Juliano and Ling as a TM protein, which was overexpressed in CHO cells that had acquired resistance to the effects of cytotoxic drugs. P-gp is constitutively expressed in nearly all barrier tissues. Techniques involving Northern blots or Western blots with monoclonal antibodies such as C219 and MRK 16 have been used extensively to determine the tissue distribution of P-gp. Pharmacologically, P-gp plays a role in preventing intestinal drug absorption, brain entry, and in eliminating drugs by excretion into bile and urine.
