MDR1

MDR1, also known as P-glycoprotein, is an ATP-binding cassette (ABC) transporter that in humans is encoded by the ABCB1 gene (formerly MDR1). It is widely expressed, notably in the intestinal epithelium, liver, kidney, and endothelial cells of the blood–brain barrier, where it exports a diverse range of hydrophobic compounds out of cells. The protein uses ATP hydrolysis to drive substrate efflux.

Substrates include many anticancer drugs (taxanes, anthracyclines, vinca alkaloids), as well as steroids, antibiotics, and other xenobiotics. By limiting drug absorption and promoting excretion, MDR1 modulates pharmacokinetics and contributes to multidrug resistance in tumors and to protective barrier functions in normal tissues.

Genetic variation in ABCB1 influences transporter expression and function. The C3435T (rs1045642) and G2677T/A (rs2032562) polymorphisms have been studied for associations with drug response, though findings are inconsistent. Drug–drug interactions with transporter inhibitors can alter the distribution and clearance of MDR1 substrates; clinical implications include dose adjustments and avoidance of certain combinations.

In veterinary medicine, a well-known mutation in the MDR1 gene (ABCB1) in some dog breeds leads to deficient P-gp function at the blood–brain barrier, causing sensitivity to ivermectin and other macrocyclic lactones. Genetic testing and breed-specific guidelines help prevent toxicity. Ongoing research elucidates mechanisms and potential inhibitors to modulate MDR1 activity.