ADME

ADME is an acronym in pharmacokinetics and pharmacology for Absorption, Distribution, Metabolism, and Excretion, and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug levels and kinetics of drug exposure to the tissues and hence influence the performance and pharmacological activity of the compound as a drug :

Absorption

Before a compound can exert a pharmacological effect in tissues, it has to be taken in to the bloodstream — usually via mucous surfaces like the digestive tract (intestinal absorption). Uptake into the target organs or cells needs to be ensured, too. This can be a serious problem at some natural barriers like the blood-brain barrier . Factors such as poor compound solubility, chemical instability in the stomach, and inability to permeate the intestinal wall can all reduce the extent to which a drug is absorbed after oral administration. Absorption critically determines the compound’s bioavailability. Drugs that absorb poorly when taken orally must be administered in some less desirable way, like intravenously or by inhalation (e.g. zanamivir ).

Distribution

The compound needs to be carried to its effector site, most often via the bloodstream. From there, the compound may distribute into tissues and organs, usually to differing extents.

Metabolism

Compounds begin to be broken down as soon as they enter the body. The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new compounds called metabolites. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of parent drug and this usually reduces the effects on the body. Metabolites may also be pharmacologically active, sometimes more so than the parent drug.

Excretion

Compounds and their metabolites need to be removed from the body via excretion, usually through the kidneys (urine) or in the feces. Unless excretion is complete, accumulation of foreign substances can adversely affect normal metabolism.

Sometimes, the potential or real toxicity of the compound is taken into account (*ADME-Tox* or ADMET). When the Liberation of the substance (from protective coating, or other excipients ) is considered, we speak of LADME.