Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and eventually into the urine. This process is facilitated by ATP-dependent efflux transporters localized in the apical membrane of the renal tubule cells. Similarly, the organic cation transporter helps transfer basic drugs from the peritubular capillaries and into the urine. This transporter operates by utilizing P-glycoproteins expressed on the apical membrane, which aid in moving drugs down their concentration gradient and into the tubular fluid. This process allows the elimination of basic drugs from the body. Different drugs potentially compete for the same transport system because these transporters are not selective. This competition occurs when multiple drugs bind to the transporter simultaneously, reducing transport efficiency for each drug. As a result, the tubular secretion of drugs can be slowed down when competing drugs are present. The competitive interaction between drugs can be harnessed to extend the effect of certain medications. For example, the effect of penicillin is prolonged by co-administering it with probenecid. Both drugs compete for the same acid transporter. When probenecid is administered alongside penicillin, it occupies the transporter and slows the secretion of penicillin into the urine. Consequently, the presence of penicillin in the bloodstream is prolonged, allowing for a more sustained therapeutic effect.