Drug elimination is the process by which pharmaceutical substances are removed from the body. All drugs are eventually eliminated from the body, although there are various pathways that may be involved in the process. Some drugs undergo metabolism before being excreted, whereas other drugs are largely eliminated intact in the original dosage form.
The kidneys are responsible for the majority of excretion of water-soluble substances. The biliary system can also excrete drugs that are not reabsorbed from the gastrointestinal tract.
In most cases, the amount of excreted drug in the intestine, saliva, sweat, breast milk and lungs is negligible. However, some volatile anesthetics can be exhaled via the lungs. Also, even small drug concentrations in breast milk of lactating women may affect a breastfeeding infant.
Renal Excretion
Approximately 20% of the plasma is filtered through the glomerulI into the kidney ultrafiltrate. Most of the water and electrolytes is then passively or actively reabsorbed into blood from the renal tubules, and are not excreted in the urine. In contrast, polar compounds, such as most drug metabolites, are not able to diffuse back into the circulation so easily, and are excreted from the body in the urine.
The renal excretion of drugs typically decreases with age, and the renal clearance of an individual at the age of 80 is considered to be approximately half of what it was at the age of 30. As a result, drugs that are predominantly excreted by the kidneys may require to be administered at half the dose for elderly patients, to reduce the risk of adverse effects.
Various factors can affect renal excretion, such as:
- Drugs that are bound to large proteins in the plasma cannot be filtered out of the plasma, and hence remain in the blood circulation.
- Un-ionized drugs and metabolites are usually able to diffuse out of the renal tubule and are reabsorbed into the blood.
- Urine pH can alter reabsorption and excretion due to the effect that it has on the ionization of weak acids and bases.
- Metabolic inhibitors can alter the active tubular secretion of many drugs, particularly when the drug concentration is high.
Biliary Elimination
Some drugs and metabolites can be excreted in the bile because they cross the biliary epithelium via active secretory transport. When the concentration of the drug in the body is high, the secretory transport carriers can become saturated and the excretion reaches an upper limit.
Drugs that are excreted through bile are large, with a molecular weight <300 g/mol, and usually have polar and lipophilic groups. Smaller molecules are usually excreted in the kidneys.
Other Forms of Elimination
Some drugs can be excreted to varying extents in the saliva, tears, feces, sweat, breast milk and by exhalation from the lungs. However, this usually only occurs in small amounts. The excretion of drugs in breast milk can be a concern for lactating mothers because of the exposure this causes to infants who are breastfeeding.
Pharmacokinetic Parameters for Excretion
The pharmacokinetic parameters for drug excretion include:
- Rate of elimination: renal excretion + extrarenal elimination
- Clearance: rate of drug elimination / plasma drug concentration OR elimination rate constant x apparent volume of distribution
- Elimination rate constant: drug elimination rate / amount of drug in body OR clearance / volume of distribution
- Biologic half-life for first order elimination drugs: 0.693 / elimination rate constant
Pharmacokinetics 5 - Excretion
References
Further Reading
New insights into the mechanisms of efavirenz-induced neurotoxicity