What Is ADME?
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ADME is the abbreviation for Absorption, Distribution, Metabolism and Excretion. ADME studies are designed to investigate how a chemical (e.g. a drug compound) is processed by a living organism. Toxicology tests are often a part of this process, yielding the acronym ADMET.
What are the four steps of pharmacokinetics?
Pharmacokinetics is a specific branch of pharmacology that studies what the body does to a drug. Pharmacokinetic studies evaluate:
- The rate that a chemical is absorbed and distributed
- The rate and pathways of drug metabolism and excretion
- The plasma concentration of a drug over time
ADME are the four steps of pharmacokinetics. Let us break down what each of these steps involves.
Absorption describes how a chemical enters the body. Absorption relates to the movement of a chemical from the administration site to the bloodstream.
There are four main routes of administration:
- Ingestion through the digestive tract
- Inhalation via the respiratory system
- Dermal application to the skin or eye
- Injection through direct administration into the bloodstream
Only injected compounds enter directly into the systemic circulation. For drugs administered through ingestion, inhalation or dermal contact, the chemicals must cross a membrane before entering the bloodstream.
There are 4 ways through which a chemical can cross a membrane and enter the bloodstream.
- Passive diffusion: When a molecule moves from an area of high concentration to an area of low concentration. This is the most common way a drug is absorbed.
- Facilitated diffusion: When a molecule moves from an area of high concentration to one of low concentration with the help of carrier proteins in the membrane.
- Active diffusion: An energy-dependent process during which a molecule requires energy in the form of ATP to cross a membrane.
- Endocytosis: When a larger drug is transferred through a membrane via invagination of the membrane.
The route of administration influences bioavailability, which is a measure of how much of a drug is absorbed in an unchanged form. You can find the bioavailability by measuring the plasma drug concentration over time. Only intravenous administration results in 100% bioavailability. Drugs administered in other ways will have reduced bioavailability. Not all of the compound will make it into the bloodstream. For instance, a drug that is ingested first undergoes metabolism during which some of the drug is excreted before entering the bloodstream.
Once a drug has been absorbed, it moves from the absorption site to tissues around the body. This distribution from one part of the body to another is typically accomplished via the bloodstream, but it can also occur from cell-to-cell.
Researchers examine where the chemical travels to, the rate at which it arrives to certain sites, and the extent of the distribution to help determine efficacy. Some compounds move easily, while others do not. Factors such as blood flow, lipophilicity, tissue binding, and molecular size influence distribution.
Drug metabolism is the biotransformation of a drug by organs or tissues (primarily the liver, kidney, skin or digestive tract) so that the drug can be excreted. To facilitate removal via feces or urine, the drug compound is altered to become more water-soluble.
Chemical metabolism can result in toxicity, for instance by creating damaging biproducts or a toxic metabolite. Scientists map out the specific metabolic pathways of a drug candidate, something called adverse outcome pathways (AOPs). AOPs provide data needed to determine the potential safety or toxicity of a drug.
Drug metabolism and interaction data provide researchers with the information they need to determine the likelihood of drug–drug interactions (DDIs). Anticipating drug interactions is essential for safe pharmaceutical development.
Excretion is the process by which the metabolized drug compound is eliminated from the body. Researchers want to know how rapidly the drug is excreted and what pathway it takes to exit the body. Most drug excretion occurs as feces or urine. Other excretion methods include through the lungs or in sweat through the skin. Molecular size and charge influence the excretion pathway.
Not every drug compound is fully excreted. When the chemical or metabolic by-products bioaccumulate, adverse effects can occur. Lipid-soluble compounds are more prone to bioaccumulate compared to water-soluble compounds.
Why is ADME important?
In drug discovery and development, researchers must examine the activity of a drug in the body to assess safety and toxicity. Drug metabolism and pharmacokinetics studies, such as ADME and toxicology studies, are a critical step in this process. The data collected tells researchers if a drug is viable and provides specific targets for future research and development.
Advances in the field have precipitated the rise of personalized ADME approaches, where factors such as a patient's genome or even the time of day during which drugs are administered are considered. Computational techniques are often used to assist these more precise studies.