tubular secretion

If filtration is a passive screen, tubular secretion is an active pump that grabs drug directly out of the blood and shoves it into the urine. It does not wait for the glomerulus; it works on drug still circulating in the capillaries that wrap around the tubule, including drug that is bound to plasma proteins.

The work is done by transporter proteins in the cells of the proximal tubule, chiefly two families: organic anion transporters that secrete acidic drugs such as penicillins and methotrexate, and organic cation transporters that secrete basic drugs such as metformin. Because secretion uses carriers, drugs sharing the same transporter can compete with one another, and the system can be saturated at high concentrations.

Secretion is powerful: it can clear drug faster than filtration alone, which is why some drugs have a renal clearance higher than the glomerular filtration rate. Competition is also exploited deliberately, as when probenecid blocks the anion transporter to slow the loss of a co-administered drug.