ADME 826690 201038596 2008-03-26T12:12:41Z 89.235.148.154 /* External links */ {{TOCright}} '''ADME''' is an [[acronym]] in [[pharmacokinetics]] and [[pharmacology]] for [[absorption (pharmacokinetics)|'''a'''bsorption]], [[distribution (pharmacology)|'''d'''istribution]], [[metabolism|'''m'''etabolism]], and [[excretion|'''e'''xcretion]], and describes the disposition of a [[pharmaceutical]] [[Chemical compound|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]]: ===Absorption=== :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 [[route of administration|be administered]] in some less desirable way, like [[intravenous therapy|intravenously]] or by [[inhalation]] (e.g. [[zanamivir]]). ===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. ===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 [[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. ===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. 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 [[excipient]]s) is considered, we speak of '''LADME'''. [[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== * [[Pharmacokinetics]] * [[Cheminformatics]] * [[Combinatorial chemistry]] * [[Pharmacology]] * [[Solubility]] * [[blood plasma|Serum]] * [[Lipinski's Rule of Five]] * [[Bioavailability]] * [[Caco-2]] * [[Simcyp Simulator]] ==References== *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?, [http://dx.doi.org/10.1016/j.drudis.2006.06.013 Drug Discov Today]. 2006 Aug;11(15-16):700-7, [http://www.vcclab.org/~itetko/DDT.pdf pre-print]. == External links == * [http://www.netsci.org/Science/Special/feature06.html The Emerging Role of A.D.M.E. in Optimizing Drug Discovery and Design] * [http://www.q-lead.com/adme_pk ADME prediction] {{Medicinal chemistry}} [[Category:Pharmacokinetics]] [[Category:Medicinal chemistry]] [[ca:(L)ADME]] [[pl:LADME]] [[sl:LADME]] [[th:ดกผข]]