Drug metabolism phase 1 and phase 2

The content has been concisely summarized to help understand various steps involved in the phase 1 and pase 2 metabolism processes of xenobiotics. These reactions include hydrolysis, reduction, and oxidation. Metabolism or biotransformation the conversion from one chemical form of a substance to another. Concluding, culturing heparg cells in the amcbal yields substantial phase 1 and phase 2 drug metabolism, while maintaining high viability, rendering dmso addition superfluous for the promotion of drug metabolism. Metabolism drug metabolism is the anabolic and catabolic breakdown of drugs by living organisms. For an individual drug, impact of ontogeny on clearance is greatest when pgx contribution 0, and fraction metabolized 1 quantitative proteomic data may allow refinement of equations describing. Hence, drug metabolism is an important aspect of living systems. Phase ii metabolism pharmacology medbullets step 1. Types of phase 1 and phase 2 metabolism associated enzymes and cofactors. Despite these and other shortcomings 91, the traditional classification in phase 1 and 2 reactions remains helpful to structure the wide range of. 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. Metabolites can increase elimination and reduce the effect of drug. During phase 1, the inactive drug is made active by a set of drug metabolising enzymes. Difference between phase i and phase ii metabolism.

Monoamine oxidase, fad02, deamination, primary, secondary, and tertiary amines. Drug metabolism is the phase of biochemical transformation of the drug. Interactions can lessen or magnify the desired therapeutic effect of a drug, or may cause unwanted or unexpected side effects. The final product is oxidized drug and water together, the cyp450mediated reactions account. The enzymecatalyzed reactions of phase i metabolism bind oxygen, hydrogen, water, or amino acids to the lipophilic drug molecule to expose or introduce a hydroxyl oh, amino nh 2, sulfhydryl sh, or carboxyl cooh polar functional group, and thus, result in a modest increase in the parent drugs water solubility. Drug metabolism is often considered during drug design. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Learn vocabulary, terms, and more with flashcards, games, and other study tools. 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.

Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed by several enzymes including cytochrome p450. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. Conjugation is very important, as this is the phase that increases the water solubility of the drug, which is needed to allow excretion of the drug. Also, there is a wide variety of reactions that can be called metabolism. Phase 1 and or phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1 metabolism followed by phase 2 metabolism. There are many drugs that alter the normal action of drug metabolizing enzymes. View the rest of my pharmacology videos in order below.

Drugs get metabolize through various types of metabplic reactions, in this video, there is explanation about these reactions with examples. Modeling of phase 2 metabolism enzymes drug metabolism. 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. Phase ii metabolism glucuronidation, acetylation, and sulfation reactions conjugation reactions that increase water solubility of drug with a polar moiety glucuronate, acetate, and sulfate, respectively. This is typically due to the production of the new protein drug metabolizing enzyme. Introduction to phase i and ii metabolisms phase i. 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. Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion. Introduction of a polar functional group or modification of an existing functional group in a drug molecule such that it becomes more polar. Phase i metabolism definition of phase i metabolism by. Xenobiotic metabolizing enzymes are grouped into those that carry out. Phase i reactions convert the parent drug into more polar metabolites through introduction or exposing oh, sh, or nh2 functional groups. The biochemical reactions are known as metabolic pathways and involve enzymes that transform one substance into another substance, either.

Phase i reactions involve formation of a new or modified functional group or cleavage oxidation, reduction, hydrolysis. For example, phase i metabolism converts acetonitrile to hoch2cn, which rapidly dissociates into formaldehyde and. Phase ii drug metabolising enzymes are mainly transferases. The term metabolism is commonly used probably because products of drug transformation are called metabolites. Therefore, amcbal culturing makes the heparg cells more suitable for testing metabolism and toxicity of drugs. In phase 2, the active drug is made inactive and transformed in such a way that it is now suitable for excretion through urine and bile. Phase 1 andor phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1. The content is so presented to allow the reader to compare various processes simultaneously and can easily memorize and learn about the topic. Biotransformation is the chemical modification or modifications made by an organism on a chemical compound.

For instance, a drug containing a benzene group may undergo phase i reactions e. Drug metabolism phase 2 conjugation reactions medicinal chemistry 3rd stage 1. Phase i reactions of drug metabolism involve oxidation, reduction, or hydrolysis of the parent drug, resulting in its conversion to a more polar molecule. The whole range of biochemical processes that occur within an organism, metabolism consists both of anabolism and catabolism the buildup and breakdown of substances, respectively. These reactions may be grouped into phase 1 and phase 2 type reactions. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Phase ii reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine. What phase 1 reaction is mainly performed by the cytochrome p450 enzymes also called mixedfunction enzymes. This chapter focuses on phase ii biotransformation reactions also called. This results in activation or inactivation of the parent drug. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. 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.

And as stated in rau, metabolites can be more toxic than the drug the metabolism of acetaminophen tylenol in the liver is hepatotoxic. Induction of phase i, ii and iii drug metabolismtransport by xenobiotics. Phase 2 drug metabolism enzymatic conjugation reaction in the intestine and liver to form mostly inactive polar metabolite that is excreted in urine or feces mostly in the cellular cytosol except glucuronidation enzyme, which is a microsomal enzyme. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar. Drug metabolisminteractions definition drug metabolism is the process by which the body breaks down and converts medication into active chemical substances. Metabolic processes drugs may be metabolized by a wide variety of enzymes located throughout the body. Glutathione gsh or mercapturic acid conjugations 5. This is called conjugation and the product is called a conjugate. 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.

In such cases, called firstorder elimination or kinetics, the metabolism rate of the drug is a constant fraction of the drug remaining in the body ie, the drug has a specific halflife. 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. The drug metabolism process occurring in organs other than the figure 1. Although phase i drug metabolism occurs in most tissues, the primary and. Induction of phase i, ii and iii drug metabolismtransport. Phase i reactions of drug metabolism involve oxidation, reduction. For example, if 500 mg is present in the body at time zero, after metabolism, 250 mg may be present at 1 hour and 125 mg at 2 hours illustrating a half. The drug metabolism happening in the liver is termed as hepatic metabolism. Specific activity determined by a fluorescent product generated from an. Precautions drugs can interact with other drugs, foods, and beverages.

Phase 1 metabolism by cyps and phase 2 conjugation to a glucuronide is one of the most common drugmetabolism combinations. This is done by adding a functional group oh here on to the drug compound. Phase i modification, phase ii conjugation and phase iii further modification and excretion and all three phases actively involve to detoxify and remove xenobiotics from the cells. What drugs metabolism has phase 2 preceding phase 1. The second phase of drug metabolism is conjugation, which is a phase i metabolite joining to another compound. Phase ii reactions involve conjugation with an endogenous substance eg, glucuronic acid, sulfate, glycine. The insertion of a hydroxyl group allows a phase 2 conjugation reaction to take place with the polar sulphate group being added. The metabolism phase is absent for the few drugs that are not transformed. It is highly variable among drugs and depends on biological conditions. Phase ii biotransformation reactions also conjugation reactions generally serve as a detoxifying step in drug metabolism. Cyps are predominantly expressed in the liver, but can also occur in small intestine reducing drug bioavailability, lungs, placenta, and kidneys 2. In addition to the liver, every biological tissue of the body has the ability to metabolize drugs.