Drug excretion is the process by which drugs and their metabolites are removed from the body, primarily via the kidneys, but also through the liver, lungs, skin, and intestines. Efficient excretion is essential to prevent drug accumulation and toxicity.
- Glomerular Filtration Rate (GFR): Higher GFR increases drug filtration and excretion. Reduced kidney function, as in chronic kidney disease, decreases clearance, requiring dose adjustments.
- Tubular Reabsorption: Lipophilic drugs are more likely to be reabsorbed from the renal tubules, while hydrophilic drugs are excreted more easily.
- Active Tubular Secretion: Some drugs are actively secreted into the renal tubules via transport proteins like OAT and OCT, aiding elimination.
- Acidic Drugs: Excreted more efficiently in alkaline urine (e.g., salicylates) due to increased ionization and decreased reabsorption.
- Basic Drugs: Excreted more efficiently in acidic urine (e.g., amphetamines) as they are more ionized.
- Protein Binding: Only unbound drugs are filtered through the glomerulus. Highly protein-bound drugs are retained in the bloodstream.
- Drug Displacement: Drugs displaced from plasma proteins (e.g., by other drugs) have an increased free fraction, enhancing excretion.
- Biliary Excretion: Drugs and metabolites can be excreted into bile, entering the intestines for elimination.
- Enterohepatic Circulation: Some drugs reabsorbed from the intestines (e.g., oral contraceptives) have prolonged effects.
- Molecular Size: Smaller molecules are filtered more easily through the glomerulus, while larger molecules may require alternative pathways, such as biliary excretion.
- Lipid Solubility: Lipid-soluble drugs are more likely to be reabsorbed from the renal tubules, while water-soluble drugs are more readily excreted.
- Infants: Immature kidneys and liver function slow drug excretion.
- Elderly: Reduced renal and hepatic function can delay drug excretion, increasing the risk of accumulation and toxicity.
- Renal Disease: Reduces the body's ability to excrete drugs, especially those eliminated primarily through the kidneys.
- Hepatic Disease: Affects drug metabolism and biliary excretion, potentially prolonging drug action.
- Heart Failure: Reduces blood flow to the kidneys and liver, decreasing excretion rates.
- Competition for Renal Transporters: Drugs can compete for renal transporters, such as probenecid inhibiting penicillin secretion, prolonging its effect.
- pH Modifiers: Drugs that alter urinary pH can impact the excretion of other drugs (e.g., sodium bicarbonate alkalizes urine, enhancing acidic drug excretion).
Intravenous and oral routes can influence drug distribution and the amount that reaches organs involved in excretion.