- The ADME principle represents the four fundamental processes that describe a drug’s journey through the body: Absorption, Distribution, Metabolism, and Excretion. Each process plays a crucial role in determining a drug’s effectiveness and safety profile.
- Absorption is the process by which a drug moves from its site of administration into the bloodstream. For oral medications, this primarily occurs in the gastrointestinal tract, where factors such as pH, blood flow, surface area, and the drug’s chemical properties (like lipophilicity and molecular size) significantly influence absorption rates. The first-pass effect, where drugs are partially metabolized by the liver before reaching systemic circulation, can significantly reduce bioavailability. Different routes of administration (oral, sublingual, transdermal, intramuscular, etc.) offer varying absorption profiles and bioavailability.
- Distribution refers to the dispersion of drugs throughout the body’s tissues after entering the bloodstream. This process is influenced by several factors, including blood flow to different organs, tissue binding affinity, protein binding in plasma, and the drug’s ability to cross biological barriers like the blood-brain barrier. The extent of distribution is quantified by the volume of distribution (Vd), which relates the total amount of drug in the body to its plasma concentration. Some drugs may accumulate in specific tissues (tissue reservoirs) or have difficulty reaching certain areas (sanctuary sites).
- Metabolism involves the biochemical modification of drugs, primarily in the liver, to form more water-soluble compounds that can be more easily excreted. This process occurs in two main phases: Phase I reactions (oxidation, reduction, hydrolysis) and Phase II reactions (conjugation). The cytochrome P450 enzyme system plays a major role in Phase I metabolism, while various transferases facilitate Phase II reactions. Genetic variations in metabolic enzymes can lead to significant differences in drug processing between individuals. Some metabolites may be active, contributing to the drug’s therapeutic effects or toxicity.
- Excretion is the final step where drugs and their metabolites are eliminated from the body. The kidneys are the primary route of excretion for most drugs, though some are eliminated through bile (enterohepatic circulation), exhaled air, sweat, or other routes. Renal excretion involves glomerular filtration, active tubular secretion, and passive reabsorption. The rate of elimination is often expressed as half-life, which helps determine appropriate dosing intervals. Factors affecting excretion include kidney function, urine pH, and blood flow to excretory organs.
- Understanding ADME principles is essential for:
- Drug development and optimization
- Determining appropriate dosing regimens
- Predicting drug-drug interactions
- Adjusting doses for special populations (elderly, renal/hepatic impairment)
- Understanding variations in drug response between individuals
- Developing new drug delivery systems
