ADME is the four-letter abbreviation (acronym) forabsorption,distribution,metabolism, andexcretion, and is mainly used in fields such aspharmacokinetics andpharmacology. The four letter stands for descriptors quantifying how a given drug interacts within body over time. The term ADME was first introduced in the 1960s, and has become a standard term widely used in scientific literature, teaching, drug regulations, and clinical practice.[1]
ADME, describes thedisposition of apharmaceuticalcompound within anorganism. The four criteria all influence thedrug levels and kinetics of drug exposure to the tissues and hence influence the performance andpharmacological activity of the compound as adrug. Sometimes,liberation and/ortoxicity are also considered, yielding LADME, ADMET, or LADMET.
For a compound to reach a tissue, it usually must be taken into thebloodstream – often viamucous surfaces like thedigestive tract (intestinal absorption) – before being taken up by the target cells. Factors such as poor compound solubility, gastric emptying time, intestinal transit time, 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'sbioavailability. Drugs that absorb poorly when taken orally mustbe administered in some less desirable way, likeintravenously or byinhalation (e.g.zanamivir).Routes of administration are an important consideration.
The compound needs to be carried to its effector site, most often via the bloodstream. From there, the compound may distribute into muscle and organs, usually to differing extents. After entry into the systemic circulation, either byintravascular injection or by absorption from any of the various extracellular sites, the drug is subjected to numerous distribution processes that tend to lower its plasma concentration.
Distribution is defined as the reversible transfer of a drug between onecompartment to another. Some factors affecting drug distribution include regional blood flow rates, molecular size, polarity and binding to serum proteins, forming a complex. Distribution can be a serious problem at some natural barriers like theblood–brain barrier.
Compounds begin to break down as soon as they enter the body. The majority of small-molecule drug metabolism is carried out in the liver byredox enzymes, termedcytochrome P450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new compounds calledmetabolites. 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 (seeprodrug).
Compounds and theirmetabolites need to be removed from the body viaexcretion, usually through thekidneys (urine) or in the feces. Unless excretion is complete, accumulation of foreign substances can adversely affect normal metabolism.
There are three main sites where drug excretion occurs. The kidney is the most important site and it is where products are excreted through urine. Biliary excretion or fecal excretion is the process that initiates in the liver and passes through to the gut until the products are finally excreted along with waste products or feces. The last main method of excretion is through the lungs (e.g. anesthetic gases).
Excretion of drugs by the kidney involves 3 main mechanisms:
Sometimes, the potential or realtoxicity of the compound is taken into account (ADME-Tox orADMET). Parameters used to characterize toxicity include the median lethal dose (LD50) andtherapeutic index.
Computational chemists try to predict the ADME-Tox qualities of compounds through methods likeQSPR orQSAR.
Theroute of administration critically influences ADME.