Drug excretion

The kidney is the principal drug-excreting organ. The three components of renal excretion, i.e. glomerular filtration, secretion, and reabsorption, are introduced in a brief video from Handwritten Tutorials (see the Learning Resources at the end of this topic). All renally excreted drugs reach urine via glomerular filtration. Many drugs additionally are secreted into the proximal tubule through the opportunistic (molecular similarity-based) use of organic cation and anion transporters. Lipophilic drugs are additionally secreted into the proximal tubule via passive diffusion, as they can easily cross the membranes of nephron cells. 

Passive diffusion is also the main mechanism of drug reabsorption from the nephron. Least affected are hydrophilic, i.e. polar or ionized drugs, due to their inability to cross the membranes of nephron cells. Reducing reabsorption via increasing hydrophilicity is the primary task of hepatic drug metabolism. Furthermore, physiological or induced changes of the urinary pH value alter the reabsorption of drugs capable of ionization. For example, an accidental overdose of acetylsalicylic acid (aspirin) is treated with bicarbonate infusion. The resulting urine alkalinization favors the ionized aspirin form, which is incapable of passive diffusion-mediated reabsorption (“ion trapping”, in this case in the nephron lumen), increasing its elimination rate. 

In most people renal drug excretion decreases with age, chiefly due to the physiological decline of the glomerular filtration, but also as a result of various kidney diseases. To avoid accumulation-dependent toxicity, dosing of renally excreted drugs characterized by small therapeutic indices must be appropriately reduced in such patients. Enhanced drug excretion is in turn observed upon decreased plasma protein binding, as only the unbound drug fraction undergoes filtration and secretion. A typical situation is the co-administration of two drugs competing for the same plasma protein binding sites (see the Drug Distribution topic above). Providing normal renal function, the excess of free drugs is rapidly excreted without accumulation and toxicity.     

Excretion with the bile (and thereby with feces), sweat, exhaled air, saliva, and breast milk play a much smaller role compared to urine. An exception is the excretion of volatile anesthetics with exhaled air. The particular importance of the excretion via breast milk lies in the toxic effects of some drugs on the breastfeeding infant. Note that substance-specific portions of orally administered drugs are removed with feces without entering the circulation. This is due to their incomplete absorption from the gastrointestinal tract. In contrast, some drugs undergo multiple cycles of absorption and excretion with the bile (enterohepatic circulation).