After metabolism (or sometimes directly if they are already sufficiently water-soluble), drugs and their metabolites are excreted from the body.
The kidneys are the primary route for most water-soluble agents.
Basic Renal Anatomy & Physiology
Each kidney consists of about a million nephrons, which are the functional units. A nephron includes:
Glomerulus: Site of filtration of plasma.
Proximal tubule: Important for active secretion and some reabsorption.
Loop of Henle
Distal tubule
Collecting duct
Processes Involved in Renal Excretion
The kidneys are the major route for drug excretion, especially for water-soluble drugs and metabolites. Renal excretion involves three main processes:
1) Glomerular Filtration
Occurs in the glomerulus where drugs with low molecular weight (<500 Da) and unbound (free) drug molecules are filtered into the renal tubule.
Factors affecting glomerular filtration:
Molecular size – Small molecules are filtered easily.
Plasma protein binding – Only unbound drugs are filtered.
Renal blood flow – Increased renal perfusion enhances filtration.
2) Tubular Reabsorption
In the proximal and distal tubules, drugs can be reabsorbed back into the bloodstream, reducing elimination.
Lipid-soluble, non-ionized drugs are easily reabsorbed, while polar, ionized drugs remain in urine and are excreted.
Urinary pH affects reabsorption:
Acidic urine favors excretion of basic drugs (e.g., amphetamines).
Alkaline urine favors excretion of acidic drugs (e.g., aspirin).
3) Tubular Secretion
Active transport in the proximal tubule secretes drugs into urine.
Two carrier-mediated transport systems exist:
Organic anion transporters (OATs) – Secrete acidic drugs (e.g., penicillin, furosemide).
Organic cation transporters (OCTs) – Secrete basic drugs (e.g., morphine, amiloride).
