ABCB1 Pharmacogenetics: Progress, Pitfalls, and Promise

In 1976, Juliano and Ling 1 reported expression of a 170 kDa protein in colchicine‐resistant Chinese hamster ovary (CHO) cells that was absent in drug‐sensitive cells. Because this protein altered cellular permeability to colchicine, the authors named it P‐glycoprotein (P‐gp). 1 P‐gp overexpression was described in tumor samples and leukemic cells. 2 High homology with bacterial transporters suggested that P‐gp was an efflux transporter, modulating intracellular xenobiotic concentrations. 3 In 1986, the gene encoding P‐gp was discovered and designated MDR1 (HUGO name ABCB1 ). 4 Immunohistochemical studies demonstrated P‐gp expression in tissues with secretory or excretory functions (liver, kidney, and gastrointestinal tract) and at blood‐tissue barrier sites, such as the blood‐brain barrier. 5 This pattern of expression indicated that P‐gp may influence xenobiotic response and toxicity, either through pharmacokinetic or pharmacodynamic effects. 6 Clinical Pharmacology & Therapeutics (2007) 81 , 265–269. doi: 10.1038/sj.clpt.6100052