Reabsorption (from filtrate)

Drugs are filtered at Bowman’s capsule and may also be secreted by transporters into the filtrate. Drugs which are in an uncharged form (i.e. a lipid-soluble form) in the filtrate can be reabsorbed back across the walls of the tubules and collecting duct, and into the blood vessels within a nephron. The degree of drug ionisation, or the portion of the drug that is in an uncharged form, will depend on the drug’s pK_a and on the urinary pH, as well as on whether the drug is a weak acid or a weak base. For example, a weak base with a pK_a of 6 would be 90% uncharged in neutral (pH 7) urine (from the Henderson-Hasselbalch equation), and so much of the drug could be reabsorbed, resulting in low renal clearance. Making the urine more acidic (e.g. to pH 6) would force more of the drug into the charged form (50% charged, based on the Henderson-Hasselbalch equation), meaning renal clearance would increase. This can be a strategy to enhance drug clearance following an overdose.

Virtually all drugs are filtered at Bowman’s capsule, and many drugs are also secreted into the filtrate. It therefore stands to reason that a drug which has very low renal clearance, or which is not cleared at all by the kidneys, must be completely, or almost completely, reabsorbed. Such drugs must be cleared by an alternative mechanism, and the liver is designed to identify and clear these more lipid-soluble compounds from the blood stream.