Clearance by secretion

Clearance by secretion (Cl_S) refers to the contribution to renal clearance of transporter-mediated secretion of acidic and basic drugs from the plasma into the filtrate. Since blood flow through (two) healthy male kidneys equals around 72 l/hour (120 ml/min or 100 ml/min/1.73 m²), and around 7 l/hour of that volume is filtered at Bowman’s capsule, the remaining 65 l/hour is approximately the maximum possible clearance by secretion (which would be the case if binding of drug to plasma proteins is negligible and if all drug in the bloodstream is secreted such that no drug leaves the kidneys in the blood, with the exception of reabsorbed drug).

Thus, a renal extraction ratio of 1 would result from secretion of all drug not removed by glomerular filtration, accompanied by zero reabsorption of drug from the filtrate.

Secretion clearance is facilitated by numerous transporters, including organic anion transporters (OAT) and organic cation transporters (OCT) which facilitate passive diffusion into tubular cells, and ATP-dependent efflux transport from tubular cells into the lumen by multidrug resistance-associated protein and P-glycoprotein.

It is possible to reduce Cl_S and thus reduce the necessary dosing rate for a drug by co-administering a compound which competes for binding to renal transporters. A drug called probenecid is an inhibitor of OAT proteins, and though it is used primarily to reduce the reabsorption of uric acid which is facilitated by OATs, it has also been used to reduce renal clearance of expensive antibiotic drugs that have high Cl_S rates.