Drug elimination refers to the processes that remove an administered drug from the body. This process involves both metabolism and excretion, with hydrophobic drugs requiring metabolic modification to make them more polar before excretion, while hydrophilic drugs can be excreted directly. The liver is the primary site of biotransformation, while the kidney is primarily tasked with excretion. Dysfunction in either organ can result in toxic concentrations of drugs or their metabolites accumulating in the body. Other factors affecting drug elimination include intrinsic drug properties, genetic variation, disease states, and first-pass metabolism.

Process of drug metabolism

Drug elimination is accomplished through either excretion of an unmetabolized drug or metabolic biotransformation followed by excretion. Hepatic metabolism occurs through two broad pathways: phase I, which involves the direct modification of the target molecule, and phase II, which entails conjugation of the target to a polar molecule. Phase I prepares the drug for phase II, but single-phase metabolism can also occur. Phase II involves covalent bonding of polar groups to nonpolar molecules to render them water-soluble for renal or biliary excretion. The first-pass effect is a feature of hepatic metabolism that plays a role in the elimination of many drugs.

Extrahepatic drug metabolism also takes place in the GI tract, kidneys, lungs, plasma, and skin. Renal excretion completes the process of elimination, with polar drugs or their metabolites getting filtered and excreted in the urine. Excretion in the bile is another significant form of drug elimination, while other pathways include the lungs, breast milk, sweat, saliva, and tears.

Clinical significance

Hepatic and renal diseases can affect drug elimination. Liver disease can compromise both phase I and II metabolic pathways, leading to increased half-lives of long-acting drugs and toxicity. Renal disorders can reduce renal function, hindering drug excretion. Age-related declines in liver and kidney function require dose adjustments when administering drugs to older patients. Nurses and healthcare teams must consider drug elimination when administering medications, especially in patients with liver or kidney pathology. Dosing adjustments and careful monitoring of adverse effects are necessary to ensure drugs remain in the therapeutic window.

Furthermore, certain drugs rely on specific metabolic pathways, such as the CYP3A4 enzyme, for elimination. The activity of these enzymes can be induced or inhibited by other substances, including pharmaceuticals, leading to changes in drug plasma concentration and potentially toxic levels.

Therefore, healthcare professionals must carefully monitor drug elimination pathways and adjust dosages accordingly, particularly in patients with liver or kidney diseases, as well as those with other pathologies that may affect drug elimination. Monitoring plasma concentrations of drugs, such as vancomycin or phenytoin, is crucial to ensuring they remain within the therapeutic range. Age-related declines in liver and kidney function also require careful monitoring and dosage adjustments to avoid toxicity.

Conclusion 

In conclusion, drug elimination is a complex process that involves both metabolism and excretion. Dysfunction in the liver or kidneys, genetic variations, and other factors can affect drug elimination, potentially leading to toxicity. Healthcare professionals must be aware of these factors and monitor drug elimination pathways to ensure proper dosages and avoid adverse effects.

References
1.Garza AZ, Park SB, Kocz R. Drug Elimination. [Updated 2022 Jul 11].  Available from: https://www.ncbi.nlm.nih.gov/books/NBK547662/

2. Almazroo OA, Miah MK, Venkataramanan R. Drug Metabolism in the Liver. Clin Liver Dis. 2017 Feb;21(1):1-20.
3.  Corsini A, Bortolini M. Drug-induced liver injury: the role of drug metabolism and transport. J Clin Pharmacol. 2013 May;53(5):463-74.
4.  Bernhardt R. Cytochromes P450 as versatile biocatalysts. J Biotechnol. 2006 Jun 25;124(1):128-45.
5. Zeng M, Yang L, He D, Li Y, Shi M, Zhang J. Metabolic pathways and pharmacokinetics of natural medicines with low permeability. Drug Metab Rev. 2017 Nov;49(4):464-476.