Sa251 What You Don’t Know about P-glycoprotein Can Hurt You (& Your Patients!)

Overview of the Issue P-glycoprotein, encoded by the MDR1 (also known as the ABCB1 gene) plays an important role in the absorption, distribution, metabolism and excretion of many drugs. It is not surprising, then, that dysfunction of P-glycoprotein increases susceptibility to drug toxicity (antiparasitic agents, anti-diarrheal drugs, chemotherapeutic drugs, acepromazine, butorphanol and others). P-glycoprotein dysfunction can occur 2 ways: (i) intrinsic Pglycoprotein dysfunction (inherited as a genetic mutation) or (ii) extrinsic or acquired Pglycoprotein dysfunction (by way of drug interaction--many drugs can inhibit P-glycoprotein function). In susceptible breeds, it is wise to perform MDR1 genotyping prior to administering drugs transported by P-glycoprotein in order to predict which dogs will experience drug sensitivity and which will tolerate routine doses of drugs. For all dog breeds, drugs that inhibit P-glycoprotein should not be used in combination with drugs that are transported by Pglycoprotein unless sufficient dose reductions are made.