tubular reabsorption

After the glomerulus filters fluid into the tubule, the body changes its mind about most of it. The tubule reclaims water, salts, glucose and other valuables, returning them to the blood. Any drug dissolved in that fluid can be carried back along with the water, like a swimmer pulled in by an undertow.

For most drugs reabsorption is passive and depends on lipid solubility and ionization. As water is reabsorbed, the drug left behind becomes more concentrated, creating a gradient that drives it back across the tubule wall. Only the uncharged, lipid-soluble form crosses easily, so the urine pH, which controls how much drug is ionized, strongly influences how much is reabsorbed versus excreted.

Reabsorption is the reason highly lipid-soluble drugs are excreted so poorly by the kidney: they are filtered, then almost entirely reabsorbed, achieving little net elimination. Metabolism to water-soluble, ionized products defeats reabsorption, and manipulating urine pH can be used therapeutically to trap a drug in the urine and speed its loss.