Although the kidneys represent the primary excretory route for most drugs, several other pathways can also contribute to drug elimination:
1) Biliary and Fecal Excretion
Many drugs, especially larger, more polar metabolites (often conjugates like glucuronides), can be excreted in the bile.
After reaching the intestine via bile, drugs or conjugates can be excreted in feces or may undergo enterohepatic recirculation (where the metabolite is deconjugated by gut flora, releasing the parent drug to be reabsorbed).
2) Pulmonary Excretion
Mainly for volatile substances (e.g., anesthetic gases, alcohol).
Passive diffusion from the blood into alveolar air.
3) Sweat and Saliva
Minor routes. Some drugs can appear in sweat or saliva, potentially causing taste disturbances (e.g., some antibiotics).
Very small fraction is excreted this way in most cases.
4) Breast Milk
Important for nursing mothers: small but significant amounts of some drugs can pass into breast milk and affect the infant.
Mechanisms include passive diffusion, and factors like the drug’s pKa, lipid solubility, and protein binding matter.
5) Skin / Hair
Primarily relevant in forensics or certain toxic exposures (e.g., heavy metals).
