ADME stands for Absorption, Distribution, Metabolism and Excretion. These are the four steps involved in pharmacokinetic studies which are designed to investigate how a drug compound is processed within the body of a living organism.
Oftentimes, toxicology tests also form a part of the ADME studies resulting in the abbreviation to be modified as ADMET.
Note that scientists use Lipinski’s rule of five and Verber’s rules to determine the pharmacokinetic properties of the drug.
Steps of ADME Explained:
- With the entry of the chemical into the body physically, absorption defines how the chemical moves from the site of administration to the bloodstream.
- This can occur in four different ways, namely:
- Passive diffusion – where the chemical moves from an area of high concentration to an area of low concentration;
- Facilitated diffusion – where the chemical moves from an area of low concentration to an area of high concentration with the aid of carrier proteins;
- Active diffusion – where the chemical needs energy in the form of ATP to cross the membrane;
- Endocytosis – where a larger drug is transferred through the invagination of the membrane.
- Movement of the drug to the tissues of the body is known as distribution.
- This can either happen via the blood stream or cell-to-cell.
- Factors that influence distribution are lipophilicity (affinity to fat making it fat soluble), blood flow, tissue binding, and molecular size of the drug.
- Biotransformation of the drug to facilitate its excretion via urine or faeces is known as metabolism.
- Chemical metabolism can oftentimes result in toxic bioproducts being produced.
- Adverse Outcome Pathways (AOPs) helps determine the safety or toxicity of the drug.
- The process by which the metabolized drug is thrown out of the body is known as excretion.
- While most metabolized drugs are excreted through urine or faeces, other pathways include, lungs and sweat.
- Not all drugs are completely excreted, some might bioaccumulate especially, the lipid soluble compounds.
Role of ADME in Drug Discovery:
- Data collected by researchers tells them if a drug is viable for not.
- It also helps determine the toxicity levels of the drug post metabolization and also due to drug-to-drug interactions.
- It helps determine the drug’s overall disposition or what the body does to a drug.
- Enables the manufacturer’s meet regulatory requirements.
- The bioavailability of the drug can be determined. The route of administration, which is either ingestion, inhalation, dermal application or injection, will determine the bioavailability of the drug i.e., the quantum of the drug that gets absorbed in an unchanged form.
- ADME at an early stage provides essential data for choosing preclinical applicants, suitable dosage forms, formulations and quickens the timeline for investigating new drug applications and as a consequence, the new drug application submission to the approving authority.
- Enables the researchers to know the half-life of the drug.
- ADME screening can decrease the proportion of drugs failing clinical trials, saving precious time and effort.
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