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ADME
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Contents
[hide]

• 1 Criteria
o 1.1 Absorption/Administration
o 1.2 Distribution
o 1.3 Metabolism
o 1.4 Excretion/Elimination
• 2 Toxicity
• 3 See also
• 4 References

• 5 External links

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.

[edit] Criteria
[edit] Absorption/Administration

Before a compound can exert a pharmacological effect in tissues, it has to be taken into
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).

[edit] 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.

[edit] 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.

[edit] Excretion/Elimination

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 sites where drug excretion occurs. The kidney is the most important site
and it is where products are excreted through urine. Biliary excretion or faecal 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 faeces. The last method of excretion is
through the lungs e.g. anaesthetic 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, sulphate conjugates) or cations such as choline,
histamine.
• Filtrate 100-fold concentrated in tubules for a favourable concentration gradient
so that it may be reabsorbed by passive diffusion and passed out through the
urine.

[edit] Toxicity
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.

Computational chemists try to predict the ADME-Tox qualities of compounds through

methods like QSPR or QSAR.

The route of administration critically influences ADME.

[edit] See also

• Pharmacokinetics
• Cheminformatics
• Combinatorial chemistry
• Pharmacology
• Solubility
• Serum
• Lipinski's Rule of Five
• Bioavailability
• Caco-2
• Simcyp Simulator
• Simulations Plus

[edit] References
• S.K. Balani; G.T. Miwa; L.S. Gan; J.T. Wu; F.W. Lee (2005). "Strategy of
utilizing in vitro and in vivo ADME tools for lead optimization and drug
candidate selection". Curr Top Med Chem 5 (11): 1033–8.
doi:10.2174/156802605774297038.
• Singh S.S. (2006). "Preclinical pharmacokinetics: an approach towards safer and
efficacious drugs". Curr Drug Metab 7 (2): 165–82.
doi:10.2174/138920006775541552.
• Tetko IV, Bruneau P, Mewes HW, Rohrer DC, Poda GI. (2006). "Can we estimate
the accuracy of ADME-Tox predictions?," (pre-print). Drug Discov Today 11 (15-
16): 700–7. doi:10.1016/j.drudis.2006.06.013.
http://www.vcclab.org/~itetko/DDT.pdf.

[edit] External links

• PubPK The Complete Pharmacokinetic Database
• The Emerging Role of A.D.M.E. in Optimizing Drug Discovery and Design
 [show]
v•d•e
Topics in Medicinal Chemistry

[show]
v•d•e
Medication > Pharmacology

Retrieved from "http://en.wikipedia.org/wiki/ADME"

Categories: Pharmacokinetics | Medicinal chemistry

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