Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and polar compounds so that they are excreted by various processes. When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily. Biotransformation an overview sciencedirect topics. Biotransformation is the chemical modification or modifications made by an organism on a chemical compound.
In addition to the liver, every biological tissue of the body has the ability to metabolize drugs. Cyp3 drug metabolism 1 subfamily, 4 genes, 2 pseudogenes. Excretion of active drug often by the kidneys, but may also be in bile, or exhaled. Limited data are available on the pharmacodynamics of drugs. Simple hydrolysis in the stomach is normally an innocuous reaction, however there are exceptions. Phase i metabolism of drug candidates can be simulated in the laboratory using nonenzyme catalysts. Metabolites formed in phase 2 are unlikely to be pharmacologically active.
Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and polar compounds so that. Cyp2c8 substrate drugs include amodiaquine, cerivastatin, dasabuvir, enzalutamide, imatinib, loperamide, montelukast, paclitaxel, pioglitazone, repaglinide, and rosiglitazone, and the. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Little overlap in substrate specificities of the two isoforms appears to exist. Often these reactions involve the introduction of polar functional groups such as oh to drug molecules to make them more hydrophilic.
The term metabolism is commonly used probably because products of drug transformation are called metabolites. Pandya 9 phases of metabolism phase 1 reaction non synthetic phase phase 2. Introduction to phase i and ii metabolisms phase i. Sep 22, 2017 metabolism is the protective biochemical process by which our bodies alter xenobiotics either enzymatically or nonenzymatically. Oxidation is the chemical reaction that occurs when apples turn brown when exposed to the oxygen in air. Oct 26, 2014 2 outline introduction history phases of metabolism phase i metabolism cytochrome p family phase ii metabolism first pass metabolism ante drug microsomal enzyme induction role of metabolism in drug discovery dr swaroop hs copyighted 3.
Pharmacokinetic interactions between drugs and botanical. Evolution of drug metabolism as a science post wwii pioneers richard tecwyn williams great britain 1942, worked on the metabolism on tnt with regard to toxicity in munitions workers. More generally, xenobiotic metabolism from the greek xenos stranger and biotic related to living beings is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organisms normal biochemistry, such as any drug. The content has been concisely summarized to help understand various steps involved in the phase 1 and pase 2 metabolism processes of xenobiotics. What are the possible metabolism of phase 1 and ph. Drug metabolism enzyme activity is typically reduced in the neonate, but rapidly develops over the first year of life. But phase i metabolism converts acetonitrile to hoch 2 cn, which rapidly dissociates into formaldehyde and hydrogen cyanide, both of which are toxic. Ppt drug metabolism powerpoint presentation free to download id. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individuals. Ppt drug metabolism powerpoint presentation free to. Overview definition consequences types phase iii in detail enzyme inductioninhibition first pass metabolism.
Phase 1 drug metabolism ghosal 1 and 2 flashcards quizlet. Siteorgans of drug metabolism the major site of drug metabolism is the liver. The cyps and fmos are composed of superfamilies of enzymes. Genetic polymorphisms, drug metabolism and drug concentrations. Often, phases 1 and 2 pathways work together to help in the removal of the xenobiotic. Many drugs are bound to blood proteins such as serum albumin the main blood protein and are not available as active drugs. Difference between phase i and phase ii metabolism compare.
Phases i and ii of the metabolism of a lipophilic xenobiotic. The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. Introduction to phase i and ii metabolisms phase i metabolism. Drug metabolism is conventionally described as consisting of phase 1 oxidation reactions, primarily mediated by cytochrome p450 enzymes in the liver, and phase 2 conjugations such as glucuronidation, sulphation and acetylation. Drugs get metabolize through various types of metabplic reactions, in this video, there is explanation about these reactions with examples. Phase 2 metabolism involves reactions that chemically change the drug or phase 1 metabolites into compounds that are soluble enough to be excreted in urine. Types of biotransformation phasei or functionalization or non synthetic. Phase ii drug metabolism is a conjugation reaction. Describe the mechanisms of drug clearance and metabolism. Protein binding attachment of the drug to blood proteins is an important factor influencing drug distribution. Intestinal mucosa, kidney, lungs, skin and adrenals intestinal mucosa intestinal wall is rich in esterases and lipases enzymes. K arthik kumar, 09bu1r0010, mlr institute of pharmacy.
During the last 1015 years, cytochrome p450 cyp 2c8 has emerged as an important drug metabolizing enzyme. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Sult1 and 2 are most important in the metabolism of drugs found in liver, kidney, intestine, in cytosol catalyze the sulfation of alcohols roh phenols main group of substrates, aroh arylamines arnh 2 nhydroxy compounds rnhoh cofactor 3phosphoadenosine5phosphosulfate, paps is in limited supply, drug can overwhelm the system. As the drug concentration increases the p1 pathway cyp is used more. Outline the phase 1 studies conducted to characterize the clinical pharmacology of a drug. This is because only watersoluble substances undergo excretion, whereas lipid soluble substances. Answer to what are the possible metabolism of phase 1 and phase 2 for the drug carbamazepine skip navigation. In part ii we will discuss the kinetics of drug metabolism and the relationship of kinetic data to the pharmacokinetics of a drug.
Metabolic organs the chemistry of drug metabolism needs an elaborate understanding it is a fascinatingand a complicatedprocess. Although there are many types of enzymes capable of biotransformation, cyps are the most. Phases of drug metabolism phase 1 drug metabolism functional conversion to polar metabolites in preparation for conjugation mostly in endoplasmic reticulum of the liver oh, nh2, sh, cooh often results in inactive metabolite, although sometimes metabolite more active prepares drug for phase 2 metabolism. It is highly variable among drugs and depends on biological conditions. Previous question next question get more help from chegg.
Tylenol can be metabolized by phase or phase 2 metabolism however the phase 2 metabolism predominates at lower concentrations of the drug. Phase ii conjugation reactions subsequent reaction in which a covalent linkage is. As explained in great detail in other chapters see 5. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2, sh or cooh to increase reactivity and slightly increase hydrophilicity. A free powerpoint ppt presentation displayed as a flash slide show on id. Page 1 drug metabolism page 2 drug metabolism metabolism biotransformation of compounds is essential for survival of the organism. Phase i and phase ii reactions of drug authorstream. The hydroxylated product produced from phase 1 reactions can also be conjugated by conjugation enzymes to more hydrophilic products, easier to excrete. View the rest of my pharmacology videos in order be. Metabolism drug metabolism is the anabolic and catabolic breakdown of drugs by living organisms. The terms in the table below are a collection of items from the lectures that you should be able to define and relate in a sentence or two to drug metabolism as set out in the notes. Phase 2 conjugation of a drug can occur in the absence of phase 1 metabolism. Phases i and ii of the metabolism of a lipophilic drug. Drug metabolism is the phase of biochemical transformation of the drug.
Phase 1 andor phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1. Jan 06, 2019 the key difference between phase i and phase ii metabolism is that the phase i metabolism converts a parent drug to polar active metabolites while phase ii metabolism converts a parent drug to polar inactive metabolites. This document is highly rated by students and has been viewed 490 times. In this phase an existing functional group already presents in the drug molecule or created by phase i metabolism such as alcohol, phenol, amine is masked or inactivated by a process of. The nats identified to date and involved in human drug metabolism include nat 1 and nat 2. Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed by several enzymes including cytochrome p450. The metabolism phase is absent for the few drugs that are not transformed. Pdf on feb 1, 2005, p david josephy and others published phase i and phase ii drug metabolism. Phase 1 metabolism can involve reduction or hydrolysis of the drug, but the most common biochemical process that occurs is oxidation.
The drug metabolism process occurring in organs other than the figure 1. What are the possible metabolism of phase 1 and phase 2 for the drug carbamazepine. Natural product dietary supplements might inhibit or induce the enzymes responsible for. The metabolism of xenobiotics is often divided into three phases. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Convert parent compound into a more polar hydrophilic metabolite by adding or unmasking functional groups oh, sh, nh2, cooh, etc. Phase i and phase ii reactions of drug authorstream presentation. Modeling of phase 2 metabolism enzymes drug metabolism. Phase ii reactions include glucuronidation, sulfation, acetylation, methylation. In this case, if 500 mg is present in the body at time zero, after metabolism, 450 mg may be present at 1 hour and 400 mg at 2 hours illustrating a maximal clearance of 50 mgh and no specific halflife. Drug metabolism pptpowerpoint presentation, medical.
Whereas phase 1 metabolism involves hydroxylation, oxidation, and reduction pathways, phase 2 metabolism involves primarily conjugation of the phase 1 metabolites with a variety of groups e. Phase i biotransformations include oxidation, reduction, and hydrolysis reactions. The first drug metabolising polymorphism was described over 40 years ago for acetylation. Drugs undergo either phase i metabolism or phase ii metabolism in addition, a drug can undergo both eg. Phase iii refers to transportermediated elimination of drug and or metabolites from body normally via liver, gut, kidney, or lung. Path of a drug after administration by any route, a drug will reach the blood stream as. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. As drug concentration increases, metabolism shifts from firstorder to zeroorder kinetics. Addition of the sulfonate moiety to the molecule of a parent compound or most often to the molecule of its metabolite originating in the oxidative phase of drug metabolism leads to formation of a watersoluble compound which is then easily eliminated from the body. Table showing examples of anaesthetic drug metabolism by cytochrome p450 system phases of metabolism metabolism of drugs is usually divided into phase 1 and phase 2. This is because of the presenceof largeamounts of many varieties of enzymes. A drug may inhibit one isoenzyme while being itself a substrate of another isoenzyme e. The drug metabolism happening in the liver is termed as hepatic metabolism. For example, phase i metabolism converts acetonitrile to hoch 2 cn, which rapidly dissociates into formaldehyde and hydrogen cyanide.
Theprimary site of drug metabolism is the smooth endoplasmic reticulum of the liver cell. Renal excretion mechanisms are low at birth, but mature over a few months. Role of cytochrome p450 2c8 in drug metabolism and. The usual classification of drug metabolism enzymes and reactions as phase i or ii is somewhat misleading, as these reactions affect some drugs in a reverse order phase ii followed by phase i, e. This is called conjugation and the product is called a conjugate. Metabolism or biotransformation the conversion from one chemical form of a substance to another.
Technology phase i and phase ii reactions of drug metabolism. Liver hepatic metabolism continues to be the most important route of metabolism for foreign ingested chemicals xenobiotics and drugs. Quantitatively, the liver and gastrointestinal tract are the most important organs of drug metabolism. Apr 02, 2020 drug metabolism pptpowerpoint presentation, medical notes edurev is made by best teachers of. Atotw 179 the role of the liver in drug metabolism 17052010 page 3 of 6. Oxidation is catalysed by cytochrome p450 enzymes and results in the loss of electrons from the drug. The product for the p1 metabolism pathway is napqi which is toxic to the liver. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion. Convert parent compound into a more polar hydrophilic metabolite by adding or unmasking. Feb 27, 2019 drug metabolism is the term used to describe the biotransformation of pharmaceutical substances in the body so that they can be eliminated more easily. Part 1 of the article covers the basics of drug metabolism. Cyp2c8 is highly expressed in human liver and is known to metabolize more than 100 drugs. Drug metabolism principles and applications 100% online. The content is so presented to allow the reader to compare various processes simultaneously and can easily memorize and learn about the topic. Phase 1 andor phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1 metabolism followed by phase 2 metabolism. Hydroxylation of an nmethyl group leads to expulsion of a molecule of formaldehyde, while oxidation of the omethyl groups takes place to a lesser extent.
Drug botanical dietary supplement interactions can include inhibition or induction of 1 p450 enzymes involved in drug metabolism, 2 udpglucuronosyl transferases, 3 other phase i and phase ii enzymes, and 4 drug transporters and drug efflux proteins. Types of phase 1 and phase 2 metabolism associated enzymes and cofactors learn with flashcards, games, and more for free. Metabolism of active drug to an inactive substance typically by the liver, but other organs kidney, lungs also metabolise some substances. Phase i reactions convert the parent drug into more polar metabolites through introduction or exposing oh, sh, or nh2 functional groups.
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