KARYEKAR ET AL RENAL INTE ACTION BETWEEN ITRACONAZOLE AND CIMETIDINE DRUG INTERACTIONS Renal Interaction Between Itraconazole and Cimetidine

T kidney plays a critical role in the removal of a wide range of endogenous substances, drugs, and metabolites from the body. Understanding the role of renal clearancemechanisms as a source of intersubject variability in pharmacokinetics is also important. It is becoming increasingly evident that carrier-mediated drug-efflux transporters in the intestine, liver, and kidney contribute to drug elimination in these organs. For example, primary active transport mechanisms are responsible for biliary excretion of anticancer drugs, endogenous bile acids, and organic anions, including glutathione and glucuronic acid conjugates. Transporters in the kidney are shown to be vital in the body’s ability to eliminate organic drugs. Within the human kidney, several drug transport proteins have been identified, including the basolateral organic anionic transporters (OATs), apical organic cationic transporters (OCTs), apical multidrug resistance protein (MRP2), and apical P-glycoprotein (P-gp). P-gp, a 170-kDa plasma membrane-bound, adenosine triphosphate (ATP)–dependent efflux protein, is likely responsible for transporting a wide variety of drugs and toxins to the extracellular environment. Drug transport has also been shown to be mediated by P-gp in other important areas of drug absorption, distribution, and elimination such as the inDRUG INTERACTIONS