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ADME is an acronym in pharmacokinetics and pharmacology for absorption, distribution, metabolism, and excretion|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:
- 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).
- 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.
- 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.
- 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 excretion 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.
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.
The route of administration critically influences ADME.
- Combinatorial chemistry
- Lipinski's Rule of Five
- Physiologically based pharmacokinetic modelling
- Balani SK, Miwa GT, Gan LS, Wu JT, Lee FW., Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection, Curr Top Med Chem. 2005;5(11):1033-8.
- Singh SS., Preclinical pharmacokinetics: an approach towards safer and efficacious drugs, Curr Drug Metab. 2006 Feb;7(2):165-82.
- Tetko IV, Bruneau P, Mewes HW, Rohrer DC, Poda GI., Can we estimate the accuracy of ADME-Tox predictions?, Drug Discov Today. 2006 Aug;11(15-16):700-7, pre-print.
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