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{{Short description|Acronym for process of disposition of pharmaceutical compounds}}
[[File:Pharmacokinetics.svg|thumb|Processes in pharmacokinetics]]
'''ADME''' is the four-letter abbreviation (acronym) for [[absorption (pharmacokinetics)|''absorption'']], [[distribution (pharmacology)|''distribution'']], ''[[metabolism]]'', and ''[[excretion]]'', and is mainly used in fields such as [[pharmacokinetics]] and [[pharmacology]]. 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.<ref>{{Cite journal |last1=Doogue |first1=Matthew P. |last2=Polasek |first2=Thomas M. |date=2013 |title=The ABCD of clinical pharmacokinetics |journal=Therapeutic Advances in Drug Safety |language=en |volume=4 |issue=1 |pages=5–7 |doi=10.1177/2042098612469335 |issn=2042-0986 |pmc=4110820 |pmid=25083246}}</ref> 

ADME describes the [[Drug Disposition|disposition]] of a [[pharmaceutical]] [[Chemical compound|compound]] within an [[organism]]. The four criteria all influence the [[drug metabolism|drug levels and kinetics]] of drug exposure to the tissues and hence influence the performance and [[pharmacological activity]] of the compound as a [[drug]]. Sometimes [[liberation (pharmacology)|liberation]] and/or [[toxicity]] are also considered, yielding LADME, ADMET, or LADMET.

== Components ==

=== Absorption/administration ===
{{Main article| Absorption (pharmacology)}}

For a compound to reach a tissue, it usually must be taken into the [[bloodstream]] – often via [[mucus|mucous]] surfaces like the [[digestive 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's [[bioavailability]]. Drugs that absorb poorly when taken orally must [[route of administration|be administered]] in some less desirable way, like [[intravenous therapy|intravenously]] or by [[inhalation]] (e.g. [[zanamivir]]). [[Routes of administration]] are an important consideration.

=== Distribution ===
{{Main article| Distribution (pharmacology)}}

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 [[intravascular]] 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 one [[Compartment (pharmacokinetics)|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 ===
{{Main article| 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 [[metabolite]]s.  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 ===
{{Main article|Excretion }}

Compounds and their [[metabolite]]s need to be removed from the body via [[excretion]], usually through the [[kidney]]s (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.

== Toxicity ==
Sometimes, the potential or real [[toxicity]] of the compound is taken into account ('''ADME-Tox''' or '''ADMET''').  Parameters used to characterize toxicity include the median lethal dose ([[LD50|LD<sub>50</sub>]]) and [[therapeutic index]].

[[computational chemistry|Computational chemists]] try to predict the ADME-Tox qualities of compounds through methods like [[Quantitative structure-property relationship|QSPR]] or [[Quantitative structure-activity relationship|QSAR]].

The [[route of administration]] critically influences ADME.

== See also ==
{{cmn|colwidth=30em|
* [[Bioavailability]]
* [[Blood plasma]]
* [[Caco-2]]
* [[Cheminformatics]]
* [[Combinatorial chemistry]]
* [[Drug metabolism]]
* [[Lipinski's rule of five]]
* [[Parallel artificial membrane permeability assay]]
* [[Simcyp Simulator]]
* [[Simulations Plus]]
* [[Solubility]]
}}

== References ==
{{refbegin}}
* {{cite journal | vauthors = Balani SK, Miwa GT, Gan LS, Wu JT, Lee FW | title = Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection | journal = Current Topics in Medicinal Chemistry | volume = 5 | issue = 11 | pages = 1033–1038 | year = 2005 | pmid = 16181128 | doi = 10.2174/156802605774297038 }}
* {{cite journal | vauthors = Singh SS | title = Preclinical pharmacokinetics: an approach towards safer and efficacious drugs | journal = Current Drug Metabolism | volume = 7 | issue = 2 | pages = 165–182 | date = February 2006 | pmid = 16472106 | doi = 10.2174/138920006775541552 }}
* {{cite journal | vauthors = Tetko IV, Bruneau P, Mewes HW, Rohrer DC, Poda GI | title = Can we estimate the accuracy of ADME-Tox predictions? | journal = Drug Discovery Today | volume = 11 | issue = 15–16 | pages = 700–707 | date = August 2006 | pmid = 16846797 | doi = 10.1016/j.drudis.2006.06.013 | url = http://www.vcclab.org/~itetko/DDT.pdf | format = pre-print }}
{{refend}}

{{Medicinal chemistry}}
{{Pharmacology}}

[[Category:Pharmacokinetics]]
[[Category:Medicinal chemistry]]