The journey of medications through the human body is a complex yet organized series of events. This journey is described by the acronym ADME: Absorption, Distribution, Metabolism, and Excretion. These four processes determine how a drug interacts with the body, influencing its effectiveness and safety. Understanding ADME provides insight into how a drug reaches its target, how long it stays active, and how it is ultimately removed.
How Drugs Enter the Body: Absorption
Absorption is the initial step where a drug moves from its administration site into the bloodstream. Common routes include oral ingestion, intravenous (IV) injection, topical application, and inhalation. To enter circulation, drugs must cross biological membranes, primarily through passive diffusion from higher to lower concentration.
Other mechanisms include carrier-mediated transport systems, which can be active (requiring energy) or facilitated (using carrier proteins without energy). A drug’s physicochemical properties, like solubility and molecular size, influence its ability to cross these membranes. For instance, lipid-soluble drugs and smaller molecules diffuse more easily.
The drug’s formulation, such as a tablet or solution, also plays a role, as solid forms must disintegrate and dissolve before absorption. For oral drugs, food in the stomach can slow gastric emptying, affecting absorption. Stomach acidity can also impact drug stability and absorption, with the un-ionized form typically diffusing more readily across cell membranes.
How Drugs Move Through the Body: Distribution
Once a drug enters the bloodstream, distribution describes its reversible movement from the blood into various tissues and organs. Blood circulation transports the drug throughout the body. The rate and extent of distribution are influenced by factors like blood flow to specific tissues.
Tissues with higher blood flow, such as the lungs, kidneys, liver, and brain, receive drugs more rapidly than those with lower blood flow, like fat. Plasma protein binding also affects distribution; many drugs bind reversibly to proteins in the blood, such as albumin. While bound, the drug is typically inactive and cannot reach its target, but the unbound “free” portion can move into tissues and exert its effect.
Specialized barriers, like the blood-brain barrier, can limit drug distribution to certain areas. This barrier, formed by tight junctions between capillary endothelial cells in the brain, restricts the passage of many substances, protecting the central nervous system. It allows only very small and lipid-soluble molecules to cross easily, making drug delivery to the brain challenging.
How Drugs are Changed: Metabolism
Metabolism is the process by which the body chemically transforms drugs into metabolites, usually to make them easier to excrete. The liver is the primary site for drug metabolism, with enzymes like the cytochrome P450 (CYP450) system playing an important role in metabolizing approximately 70-80% of all clinically used drugs.
The CYP450 system is a large family of enzymes, predominantly located in the smooth endoplasmic reticulum of liver cells, that catalyze oxidation reactions. Specific CYP450 enzymes are designated by family numbers and subfamily letters, such as CYP3A4, which metabolizes over 50% of important drugs. Metabolism can either deactivate a drug or, in some cases, activate a prodrug into its active form, as seen with codeine.
Drug-drug interactions can occur when one drug affects CYP450 enzyme activity, either by inhibiting them or inducing their production. Enzyme inhibition reduces metabolic activity, potentially leading to increased drug concentrations and a higher risk of side effects. Conversely, enzyme induction can accelerate drug metabolism, reducing drug efficacy. For example, certain foods or cigarette smoke can induce CYP1A2, an enzyme that metabolizes drugs like theophylline.
How Drugs Leave the Body: Excretion
Excretion is the removal of drugs and their metabolites from the body. The kidneys are the main organs for eliminating water-soluble substances, primarily through urine. This process involves glomerular filtration, where about one-fifth of the plasma reaching the glomeruli is filtered.
After filtration, some water and electrolytes are reabsorbed from the renal tubules, but polar compounds, including most drug metabolites, are excreted. The pH of urine can significantly influence the reabsorption and excretion of weak acids and bases. Other routes include the biliary system, which removes drugs and metabolites through bile into the feces.
Volatile substances, such as anesthetic gases, can be exhaled through the lungs. Minor routes also include sweat, saliva, and breast milk. Excretion into breast milk can be a concern due to potential exposure to nursing infants.
The Importance of ADME
Understanding the ADME process is important in drug development and patient care. This knowledge allows researchers to determine appropriate dosing regimens, predicting how much of a drug will reach its target and how long it will remain active. It also helps anticipate potential side effects and toxicity, as high concentrations of drugs or their metabolites in specific tissues can be identified.
ADME studies are important in understanding and preventing harmful drug interactions. By knowing how different drugs are absorbed, distributed, metabolized, and excreted, healthcare professionals can make informed decisions about co-administering medications. This understanding contributes to personalized medicine, where treatments are tailored to individual patients based on factors like their genetic variations and metabolic profiles, enhancing therapeutic outcomes and improving patient safety.