Liver, Kidneys, and Stomach: Drug Metabolism 

The liver, kidneys, and stomach each play a unique role in drug absorption and metabolism. Drug metabolism refers to the process by which bodily systems chemically alter drugs to change them into compounds that are easier to eliminate (5).  

Understanding drug metabolism is critical to providing effective patient care and harnessing the therapeutic effects of drugs (5). Indeed, studying each drug’s unique metabolic pathway helps medical professionals understand how a particular individual will react to a drug and predict drug interactions. In this article, we overview the basics of drug absorption and metabolism in the liver, kidneys, and stomach and explore the importance of a collaborative, interprofessional approach to drug management. 

All orally administered drugs pass through the stomach on their way to the intestines during drug absorption. Many drugs can be destroyed by the highly acidic gastric acid in the stomach and are intentionally packaged in acidic capsules to ensure that they will survive and reach the intestines (3). Drugs may be absorbed in the stomach, but drug metabolism centers on other organs, including the liver and kidneys. 

Once an oral medication has passed through the stomach and into the intestines, the epithelial cells lining the intestinal walls absorb a portion of these drugs (3). Then, the drugs that have been absorbed travel to the liver through the hepatic portal vein, where they undergo what is called first-pass metabolism (3). During first-pass metabolism, some portion of the drug is metabolized by the liver, while another portion becomes bioavailable and starts circulating through the bloodstream (3).  

Drugs are metabolized in the liver through various chemical reactions that are catalyzed by enzymes (4). There are two main phases of drug metabolism in the liver. During phase I, enzymes catalyze oxidation, reduction, or hydrolysis reactions that make the original drug more hydrophilic, or water-soluble (5). This happens because lipophilic drugs—or fat-soluble drugs—will not be able to pass into the urine and instead be reabsorbed by the bloodstream during excretion. In phase II, polar groups are attached to the drug molecule through a process called conjugation, making the drugs even more hydrophilic (5). Drugs that are already hydrophilic in their original form may be excreted without undergoing metabolism; however, hydrophobic drugs must undergo at least one of these processes in order to be eliminated from the body. 

The kidney is the primary site of drug excretion (2). Once drugs have been metabolized into polar and hydrophilic compounds, the kidney then filters these metabolites out of the bloodstream using structures called glomeruli (4). Drugs and other waste products are then reabsorbed into the urine and excreted out of the body. This is why measuring the presence of a drug or its metabolites in a person’s urine can demonstrate whether a drug was recently present in a person’s body during drug tests (3). 

Physicians, nurses, and pharmacists need to stage a collaborative approach to drug management in order to ensure that a drug has its intended therapeutic effect on a patient and to prevent dangerous drug interactions from occurring. Drugs that share the same enzymatic binding sites can “compete” for these sites, reducing the efficacy of drug metabolism and causing the level of drugs to remain high in the body (5). As a result, two or more drugs that are co-administered which share the same metabolic pathways can have negative synergistic effects (5). 

Patients with hepatic diseases affecting the liver or renal disorders affecting the kidneys can also be at risk of toxic buildup of active drugs or drug metabolites in the body due to changes in metabolism (2). Impairment of the kidneys or liver due to such diseases or age can significantly affect the safety and dosage of a drug, or even whether a drug can safely be used. Consequently, it is essential for medical practitioners to carefully consider the metabolic pathways of drugs when composing a pharmaceutical care plan for each patient. 

References 

1. Almazroo et al., “Drug Metabolism in the Liver.” Clinical Liver Disease, 2017, DOI:10.1016/j.cld.2016.08.001 

2. Garza et al. “Drug Elimination.” StatPearls Publishing, 11 Jul 2022, www.ncbi.nlm.nih.gov/books/NBK547662/ 

3. Quock, Ray. “Chapter 5: Pharmacokinetics.” Drugs and Behavior, Washington State University, 2022, n.p. 

4. Stringer, Janet. “drug.” Encyclopedia Britannica, www.britannica.com/science/drug-chemical-agent/Types-of-drugs 

5. Susa, Stephen T. and Charles V. Preuss. “Drug Metabolism.” StatPearls Publishing, Sept 2022, www.ncbi.nlm.nih.gov/books/NBK442023/