ADME

ADME is the four-letter abbreviation (acronym) for

For a compound to reach a tissue, it usually must be taken into the

Distribution

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 by

Distribution is defined as the reversible transfer of a drug between one compartment 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 the blood–brain barrier.

Metabolism

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 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 (see prodrug).

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.

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:

• Glomerular filtration
  of unbound drug.
• Active secretion of (free & protein-bound) drug by transporters (e.g. anions such as
  urate, penicillin, glucuronide, sulfate conjugates) or cations such as choline, histamine
  .
• Filtrate 100-fold concentrated in tubules for a favorable concentration gradient so that it may be secreted by passive diffusion and passed out through the urine.

The route of administration critically influences ADME.

See also

References