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14-September-2008 18:38:50 - ADME Contents 1 Absorption 2 Distribution 3 Metabolism 4 Excretion/Elimination 5 See also 6 References 7 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: 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 be administered in some less desirable way, like 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 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. 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 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. See also Pharmacokinetics Cheminformatics Combinatorial chemistry Pharmacology Solubility Serum Lipinski's Rule of Five Bioavailability Caco-2 Simcyp Simulator Simulations Plus 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. External links The Emerging Role of A.D.M.E. in Optimizing Drug Discovery and Design ADME prediction v d e Topics in Medicinal Chemistry ADME · Bioavailability · Chemogenomics · Drug design · Drug discovery · Enzyme inhibitor · Mechanism of action · New chemical entity · Pharmacodynamics · Pharmacokinetics · Pharmacology · Pharmacophore · Quantitative structure-activity relationship v d e Medication Pharmacology Pharmacokinetics ADME: Absorption - Distribution - Metabolism - Excretion Clearance Loading dose - Volume of distribution Initial - Rate of infusion Compartment - Bioequivalence - Bioavailability Biological half-life - Plasma protein binding Pharmacodynamics Toxicity Neurotoxicology - Dose-response relationship Efficacy, Potency Other fields pharmacogenetics - pharmacogenomics - Neuropsychopharmacology Neuropharmacology, Psychopharmacology Agonist: Inverse agonist Antagonist: Competitive antagonist Physiological agonism and antagonism Retrieved from http://en..org/wiki/ADME Categories: Pharmacokinetics | Medicinal chemistry Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Català Deutsch Polski SlovenÅ¡Ä?ina СрпÑ?ки / Srpski ไทย This page was last modified on 12 September 2008, at 20:3
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