Biotransformation And Elimination Of Drugs Biology Essay

Biotransformation And Elimination Of Drugs Biology Essay Liver plays a significant role in the metabolism of a large number of drugs and toxins. Hepatic drug metabolism involves various processes, broadly classified as Phase 1 (functionalisation) and Phase 2 (conjugation). Glucuronidation catalysed by UDP-glucuronosyl transferase (UGTs) plays a key role in the Phase 2 metabolism of a large number of drugs as well as many endogenous substrates, like bilirubin, steroids etc., by increasing the hydrophilicity and clearance. UGTs are versatile enzymes, in terms of broad, yet overlapping substrate specificity, presence of numerous isoforms, genetic polymorphisms etc. Biological systems are recognised to be stereoselective in nature. A large number of drugs, nearly 50% of all marketed drugs exist as either single enantiomers or racemates. Therefore stereoselective behaviour of drugs plays an important role in drug action as well as disposition (Absorption, Distribution, Metabolism and Elimination). The aim of this project is to identify the enantio-selectivity of drugs towards glucuronidation by UGT and also to identify whether enantio-selectivity is linked to specific isoforms of UGT. Furthermore, predicting the enantiomeric behaviour of drugs may also aid in rationalising in-sillico modelling of drug metabolism and thereby predicting metabolism of new chemical entities (NCEs) 1. INTRODUCTION Biotransformation and elimination of drugs from the body involves several different metabolic routes. These metabolic pathways are broadly classified into Phase 1 (functionalisation) and Phase 2 (conjugation) drug metabolism. Phase 1 metabolic pathway involves transforming the drug into a more polar functionality, through various reactions like, oxidation, reduction, hydrolysis, isomerisation and so on depending on the chemical nature of the drug. These reactions are catalysed by enzymes such as: Cytochrome P450, NADPH-cytochrome P450 reductase, acetlycholineestrase etc. Product of Phase 1 drug metabolism may then act as a substrate for Phase 2 metabolism. This phase consists of conjugation of the drug substrate with endogenous ligands leading to increased polarity, hydrophilicity and thereby elimination of the drug from body through bile or urine. Conjugation reactions include glucuronidation, glycosidation, sulfation, methylation etc. These reactions are catalysed by UDP-Glucuronosyltransferase, UDP-Glycosyltransferase, Sulfotransferase, Methyltransferase respectively. Among these, glucuronidation is the most prevalent conjugation reaction in the body. [1] 2. GLUCURONIDATION Glucuronidation is the most common reaction in Phase 2 drug metabolism. This conjugation reaction which is catalysed by UDP- glucuronosyl transferase, forms about 35% of all drugs metabolised by conjugation. This is primarily due to the abundance in living systems of UDP-glucuronic acid, the co-factor for the reaction, as well as due to the pervasive nature of the enzyme, UDP-glucuronosyl transferases (UGTs). [1] [2] The process of glucuronidation involves: I. Formation of co-factor (UDP-glucuronic acid) II. Conjugation of UDP-glucuronic acid with substrate The formation of co-factor (UDP-glucuronic acid) This consists of a two step process: 1. Formation of UDP-glucose Glucose-1-phosphate is present in high concentrations in almost all cells of the body. The first stage of glucuronidation is related to glycogen synthesis through the common intermediate, UDP-glucose. The formation of UDP-glucose occurs by addition of a Uridine 5- diphosphate (UDP), a pyrophosphate nucleotide in cells, to a molecule of Glucose-1-phosphate. The reaction is catalysed by UDP-glucose pyrophosphorylase enzyme. [1] [3] 2. Dehydrogenation of UDP-glucose to UDP-glucuronic acid The above step is followed by dehydrogenation of UDP-glucose to UDP-glucuronic acid, catalysed by the enzyme UDP-glucose dehydrogenase, in the presence of NAD+ co-factor. [3] Conjugation of the substrate with UDP-glucuronic acid Conjugation reaction involves transfer of one ÃŽÂ ±-D-glucuronic acid moiety from the co-substrate UDP-glucuronic acid (UDPGA), which act as an energy rich intermediate, to form the glucuronide conjugate of the drug molecule. The reaction is catalysed by UDP-glucuronosyl transferase (UGT) enzyme. The reaction is found to be a bimolecular nucleophilic substitution (SN2), whereby the C1 carbon of glucuronic acid, which is in ÃŽÂ ±-configuration, during its reaction with the substrate inverts to form a ÃŽÂ ²-D-glucuronide. [3] [4]. The glucuronide formed is excreted via urine or bile, depending on the chemical nature and molecular weight of the conjugate. [1] [2] The entire reaction is summarised below: Figure: 1: Glucuronidation Pathway leading to formation of ether glucuronide. [3] 2.1 PHARMACOLOGICAL RELEVANCE Based on the functional group of the substrate molecule, the following types of glucuronide conjugates may be formed; [1] O-Glucuronide They are formed from Phenols, alcohols, carboxylic acids. O-gulcuronides are chiefly excreted in to bile and may undergo entero-hepatic circulation. Examples of drugs: Morphine, Chloramphenicol, Salicylic acid, Clofibrate. Figure: 2 O- Glucuronidation of Morphine [5] [6] UGT Enzyme UDPGA N-glucuronide They are formed by the reaction of UDP-glucuronic acid (UDPGA) with amines, amides etc. E.g. Sulfanilamide, Cyproheptidine, Dapsone S-Glucuronide Reaction of thiol groups with UDPGA in presence of UDP-gucuronosyl transferase results in S-glucuronides. E.g.Disulfiram, 2-Mercapto benzothiazole C-glucuronide It is an uncommon metabolic pathway that occurs due to the direct attachment of UDPGA to the carbon skeleton of drugs. E.g. Sulfinpyrazone [1] [3] 3. UDP-GLUCURONOSYL TRANSFERASE (UGT) ENZYMES 3.1 SITE UGT enzymes are present in human beings and most other mammals. The enzyme is located in many tissues of the body, mostly in liver but also in kidney, lungs, small intestine, spleen, adrenals and skin, to a lesser extend. Inside the cell, UGTs are bound to the membranes of endoplasmic reticulum. Most of the Phase 1 metabolic enzymes, including cytochrome P450s, are located in the endoplasmic reticulum. Therefore endoplasmic reticulum is regarded as an ideal site for UGT enzymes, as it facilitates glucuronide conjugation of Phase 1 substrates. [1] 3.2 STRUCTURAL ASPECTS UDP-glucuronosyl transferase enzyme does not contain a prosthetic group. The monomeric molecular weight of the enzyme if found to be between 50- 60 kilo Daltons. The protein sequence of the enzyme shows slight variations between each individual form. A full length crystal structure of UGTs is yet to be resolved, although crystal structure of the binding domain for UDP-glucuronic acid in human UGT2B7 has been published (by Miley et.al. 2007) [1] [2] 3.3 PHYSIOLOGICAL RELEVANCE In addition to being a major enzyme involved in Phase 2 drug metabolism, UGT enzymes play a number of other roles in the body. Many endogenous compounds such as bilirubin, steroid hormones (e.g. thyroxine, triiodothyronine) and catechols (derived from catecholamine metabolism), act as substrates for UGT enzymes. All these compounds are potentially hazardous if accumulated in the body. Deficiency of UGT enzyme results in hyperbilirubinaemia. Hereditary diseases like Gilberts syndrome and Cringler-Najjars syndrome are associated with genetic polymorphisms of UGT gene [7]. Apart from disposition of endogenous toxins, the enzyme also catalyses glucuronidation of various exogenous chemicals and helps in bodys defence against toxic principles [1] [8] 3.4 MULTIPLE FORMS Various forms of UDP-glucuronosyl transferase (UGT) enzymes have been identified with the help of studies based on purification, characterization of enzymes, molecular cloning, DNA sequencing etc. About 50 vertebrate UGTs have been identified among which 19 are found in humans. UGT enzymes are divided in to families and sub-families based on similarity of their amino acid sequences. Two enzymes are in the same family if the similarity of their amino acid sequences is more than 50% and will be grouped into the same subfamily is similarity is greater than 60%. [1] [2] Nomenclature Divergent evolution and sequence similarity forms the basis of nomenclature of UGT enzymes. Name of the enzyme consists of 4 parts: [1] Root Symbol The root symbol UGT stands for UDP- glucuronosyl transferase. Family It is denoted by Arabic number. E.g. 1, 2 etc Sub-family Designated by an upper-case alphabet Individual Form An Arabic numeral is used for unique identification of the individual form of the enzyme. E.g. UGT2B4, UGT1A6 [1] Mammalian UGTs are divided in to four families: UGT1, UGT2, UGT3 and UGT8. Among these, only UGT1 and UGT2 catalyses conjugation of glucuronide and hence are discussed further. UGT1A family of enzymes are found to contain 9 functional proteins and are coded for by a single gene complex located at chromosome 2q37. The genes coding for this enzyme have common exons 2-5 (region of gene which codes for the carboxyl terminus of the enzyme) and a variable exon 1. The first exon is responsible for coding the N-terminal domain of the protein and this explains why the enzymes are substrate specific in spite of have a common C-terminal [1] [2] UGT2 enzyme family, especially UGT2B plays a vital role in the metabolism of xenobiotics and endogenous ligands. Genes coding for UGT2 family enzymes are situated on chromosome 4q13. In the case of UGT2B sub family, protein sequences at the C-terminal, gives rise to the UDP-glucuronic acid binding domain as well as helps in anchoring of the protein to membrane of endoplasmic reticulum. UGT2A subfamily is less studied and do not play a significant role in systemic metabolism. UGT2A1 is present in olfactory epithelia and to a lesser extend in cells of brain and lungs. UGT2A2 in liver and small intestine, while UGT2A3 in small intestine, liver and adipose tissue. [2] Figure: 3: Shows the Phylogenetic tree of different UGT isoenzymes. %values indicate the homology between two groups or single isoenzymes at the amino-acid level. [9] 3.5 TISSUE SPECIFICITY The various forms of UGT enzymes show tissue specificity in man. Majority of these enzymes occur predominantly in the liver, (E.g. UGT 1A1, 1A4, 1A6, 2B7 etc) while some others are found in various extrahepatic sites. An example is UGT1A10, which is present in the cells of all areas of gastrointestinal tract and hence accounts for its wide range of substrate specificity, from phenol molecules to steroids. [1] 3.6 SUBSTRATE SPECIFICITY UGTs show a wide, yet overlapping, range of specificity towards drugs and endogenous ligands. For example, glucuronidation of bilirubin is preferred by UGT1A1 and that of morphine by UGT2B7. [1] [6] Table: 1: Showing Substrate Specificity of UGT enzyme isoforms. [6] Sl.No Substrate Max. Specific enzyme activity / pmol.min-1.mg protein-1 1A1 1A3 1A4 1A6 1A8 2A1 2B4 2B7 2B15 2B17 1. Phenols 1900 239 30 2400 5300 735 0.4 5 167 38 2. Amines 1 84 540 10600 1800 22 3 0 3 Opioids 0 130 0 0 0 73 0 3462 0 4. Carboxylic acids 0 121 0 170 68 0 2 0 5. Bilirubin 400 0 2 0 0 0 0 0 0 3.7 INTERINDIVIDUAL VARIATIONS Several genetic polymorphisms in UGTs may lead to variations between individuals in the ability to glucuronidate drugs and endogenous substrates. Mutations in genes coding for UGT1 enzyme family has been identified as the cause for hereditary hyperbilirubinaemia, characterized by jaundice due to high levels of unconjugated bilirubin in the body. Further, several genetic diseases- Gilberts syndrome and Cringler-Najjars syndrome, may occur due to mutations in genes coding for UGT1A1 isoform. [1] 4. ENZYME KINETICS: Study of enzyme kinetics helps to understand the catalytic mechanism of the enzyme; role played by the enzyme in metabolism as well the rate and activity of enzyme. Michaelis Menten equation is used to describe enzyme substrate interaction and is given by: [2] k1 k 2 E + S ES E + P k-1 Where E = Enzyme, S = Substrate, P = Product Michaelis Constant Km is given by: Km = (k 2 + k -1) / k 1 Michaelis Constant Km is an indicator of affinity of substrate for the enzyme as well as the rate of enzyme activity. The kinetics of drug metabolism can also be defined using Michaelis Menten equation and may be plotted in a graph of Rate of reaction (Velocity) vs. Concentration of Substrate. Although not all enzyme substrate reactions are best described by this equation, a typical model of Michaelis Menten plot is shown below: [2] Figure: 3 Michaelis Menten hyperbolic kinetic profile. [10] Here Vmax is the maximum velocity of enzyme action. Vmax / Km is an indicator of the catalytic efficiency of the enzyme. 5. STEREOISOMERISM Molecules having the same constitution of atoms and sequence of covalent bond, but differ in their three-dimensional arrangement of atoms in space are known as stereoisomers. Stereoisomers are classified in to geometrical (cis/trans) isomers, enantiomers and diastereoisomers. Stereoisomers that are mirror images of each other and hence are not superimpossible are called enantiomers. They differ from each other only by one chiral centre. Isomers that are not mirror images are diastereoisomers. They may contain more than one chiral centre. [2] [11] While geometrical and diastereoisomers are chemically different molecules, enantiomers have identical chemical and physical properties, except for the way in which they rotate plane polarized light. Enantiomers are of great significance in therapeutics as all biological systems represent a chiral environment. Hence drug action as well as disposition (absorption, distribution, metabolism and elimination) may differ between enantiomers. [2] 5.1 DRUGS AS ENANTIOMERS As discussed above, the pharmacokinetic and pharmacodynamic properties may vary for each individual enantiomer. In 1992, United States Food and Drug Administration (US FDA) published a policy for development of new stereoisomeric drugs. Approximately 50% of all marketed drugs are found to be racemates. Although many drugs can be safely administered as racemates, some others show better efficacy and fewer side effects when administered as a single enantiomer. For example, cardiac toxicity of the local anaesthetic agent, Levobupivacaine is chiefly associated with R-enantiomer. Further, some drugs undergo chiral inversion inside the body to the other enantiomer (e.g. Ibuprofen: Non-steroidal anti-inflammatory agent) and some others undergo racemisation after administration. This is of particular concern, especially if one of the enantiomers is toxic. Hence evaluating drugs for their stereochemistry is gaining importance. [2] [12] Some examples of some single enantiomeric drugs which have gained importance, compared to their racemate counterparts are given below, due to their improved pharmacodynamic- pharmacokinetic profiles: L-DOPA: The use of levo dopa instead of racemic dopa has resulted in reduction in dose and adverse effects (nausea, vomiting, anorexia, granulocytopenia) Figure: 4: Levodopa [13] ESOMEPRAZOLE: This proton-pump inhibitor, which is the S-enantiomer of Omeprazle has shown lower first pass effect and higher plasma half life compared to the R-enantiomer, thus maintaining the intra-gastric pH above 4 for a longer duration. S-enantiomer also showed reduction in variability of response between patients. Figure: 5: Esomeprazole [14] LEVOFLOXACIN: It is a Quinolone antibiotic. As there are slight differences in disposition between enantiomers of this drug, a single S-enantiomer is preferred. Figure: 6: Levofloxacin [15] R-SALBUTAMOL (LEVALBUTEROL): S-enantiomer has shown increased hyper responsiveness of airway, sensitivity to allergens and some decrease in bronchodilator potency. While R-Salbutamol gives significantly higher bronchodilator effect and lesser side effects Figure: 7: R-Salbutamol [16] R, R-METHYLPHENIDATE: This drug is found to be ten-fold more potent than its S-enantiomer when used to treat attention deficit hyperactivity. The presystemic metabolism and disposition of the drug is enantioselective in nature. Further, the R-enantiomer shows rapid onset of action and reduced adverse effects Figure: 8 R, R-Methylphenidate [17] 6. AIM OF THE PROJECT This project aims to determine the rates of glucuronidation of enantiomeric pairs, of a wide range of drugs, to identify differences in metabolism between enantiomers of a drug and also to find out whether enantioselectivity is related to a particular family of UDP-glucuronosyl transferase (UGT) enzyme. Experiment may be done by in-vitro incubations of human recombinant UGTs or human liver microsomes with the selected substrates, followed by analysis using liquid chromatography (HPLC) equipped with a mass spectrometer for detection. [14] Laboratory analysis of enantiomers is usually done using any one of the following two methods: Chiral Chromatography, which make use of a chiral column or chiral mobile phase to separate the enantiomers. Derivatisation, of the analyte using a chiral derivative followed by separation of the resulting diastereoisomers using standard, achiral chromatographic method. But in the case of separation of drug conjugates, the analytical process is relatively simple, as the glucuronide conjugates behave just like derivatised diastereomers and hence may be separated by conventional liquid chromatography. 7. FUTURE DIRECTIONS Many late stage failures in drug development process are due to inability to predict the pharmacokinetic properties of new chemical entities (NCE) before obtaining data from clinical trials. Hence in-vitro approaches like computational (in-sillico) modelling of drug metabolism is gaining acceptance in the recent times. Many approaches such as 2D-Quantitative Structure Metabolism Relationship (2D- QSMR), 3D-Quantitative Structure Metabolism Relationship (3D- QSMR), Pharmacophore Identification as well as Non-linear pattern recognition techniques are being studied to model drug metabolising enzymes. Although predictive models for metabolism of drugs by the Phase 1 metabolising enzyme, Cytochrome P450 are widely accepted, development of effective models for UDP-glucuronosyl transferases (UGTs) catalyzed Phase 2 metabolism has received much less attention. [15] Versatility of these group of metabolic enzymes, in terms of broad but overlapping substrate specificity, drug-drug interactions, genetic polymorphisms as well as presence of a large number of isoforms are some of the challenges facing the development of predictable models for UGTs. Furthermore, apart from a few catalytically relevant amino acids, the full X-ray crystal structure of UGT enzyme is not yet elucidated. [15] [18] Depending on the parameters being modelled (e.g. Km, Vmax etc.) a number of physico-chemical and molecular descriptors, such as molecular size, shape, lipophilicity, hydrogen bonding etc., are required to model molecular recognition of substrates and catalysis by UGTs. Apart from this, study of electronic nature of the nucleophile and pKa is also significant. Since chirality plays an important role in determining metabolic behaviour of drugs, design tools may be developed that address the issue of chirality. While 2D-descriptors will only predict molecular connectivity, 3-D models predicting the enantiomeric properties of enzyme-substrate interactions might significantly improve the future of drug development process. [16] [17] 8. CONCLUSION In conclusion, many biological systems represent a chiral environment. Therefore assessing the enantioselectivity of drug metabolising enzymes plays a significant role in predicting pharmacokinetic behaviour of drugs. The present project aims at identifying the enantio-selectivity of drugs in UDP-glucuronosyl transferase (UGT) metabolism, which is an important Phase 2 (conjugation) process of drug metabolism. Furthermore, knowing the enantiomeric behaviour may help in the development of 3D-Quantitative Structure Metabolism Relationship (3D-QSMR) models for predicting drug metabolism.

Nuclear Weopons testing Essay -- essays research papers

In their effort to create a bomb that would assure destruction of enemies, the world super powers of this century have created a legacy that could presumably destroy the entire world as we know it (Schull 6). During the course of the last fifty years, nuclear weapons have continually become an increasingly detrimental threat to our own health and environment. Consequently, laws have been proposed and bills have been signed to end this senseless build-up of arsenal and testing of havoc-causing atomic was instruments. Unfortunately, enforcing such rules worldwide has proven itself to be remarkably difficult and world allies have had to use extreme caution when dealing with any and all emerging threats. In the early days of nuclear weapons production, of course, not all safety hazards were fully appreciated,and possible threats to the environment went completely unrecognized. For this reason, we continued to tryout these deadly war tools without any major concern for our future. To be sure, it is understandable that in the race to produce the atomic bomb before Hitler, such considerations would come second. What is surprising is that this negligence should persist for 50 years thereafter, in spite of the growing awareness of the threats that technology and nuclear weapons production can pose. Even the challenge of cleaning up the results of four decades of nuclear weapons production from testing should be vast enough to tell us that testing must absolutely come to a complete stop around the world. Incredible resources will be needed to dispose of 2,700 tons of spent fuel, 10,500 hazardous substances, and 100 million gallons of high-level waste; to clean up 2.3 million acres of land; and to remediate 120 million square feet of buildings on 120 sites (Day 40-41). Four major tasks can be identified: to stabilize and maintain a large number of nuclear materials and facilities; to design, build, and operate a variety of treatment facilities to prepare waste for disposal and provide safe interim storage; to manage large amounts and varieties of wastes; and to work towards environmental restoration (Mosman 13). But nuclear weapons testing has had different effects all over the world. And the "not-in-my-backyard syndrome" has come to voice opinions everywhere.-- Nobo... ... Pie Chart Below : (Source : Mollison A/08) References Day Jr., Samuel. "The big lie.," Vol. 57, Progressive, 1 Jun 1993, pp. 40. Johnson, Douglas. "Atolls and atom bombs: France's colonial design.," Vol. 45, History Today, 1 Dec 1995, pp. 8. Mollison, Andrew. "Focus on Nuclear Testing." The Atlanta Constitution, 16 Aug 1995, pp. A/08. Mosman, Jan. "Ban nuclear tests.," Vol. 339, Economist, 4 May 1996, pp. 13. Ruben, Barbara, "How to really bomb a test.," Vol. 24, Environmental Action, 1 Jan 1993, pp. 8. Schull, William J. Effects of Atomic Radiation. (New York, NY: Free Press, 1995). Sternberg, Steve. "From war's holocaust, new radiation findings," The Atlanta Journal and Constitution, 20 Mar 1993, pp. F/01. Yamazaki, James N. Children of the Atomic Bomb. (Duke University Press, 1995). Nuclear Weopons testing Essay -- essays research papers In their effort to create a bomb that would assure destruction of enemies, the world super powers of this century have created a legacy that could presumably destroy the entire world as we know it (Schull 6). During the course of the last fifty years, nuclear weapons have continually become an increasingly detrimental threat to our own health and environment. Consequently, laws have been proposed and bills have been signed to end this senseless build-up of arsenal and testing of havoc-causing atomic was instruments. Unfortunately, enforcing such rules worldwide has proven itself to be remarkably difficult and world allies have had to use extreme caution when dealing with any and all emerging threats. In the early days of nuclear weapons production, of course, not all safety hazards were fully appreciated,and possible threats to the environment went completely unrecognized. For this reason, we continued to tryout these deadly war tools without any major concern for our future. To be sure, it is understandable that in the race to produce the atomic bomb before Hitler, such considerations would come second. What is surprising is that this negligence should persist for 50 years thereafter, in spite of the growing awareness of the threats that technology and nuclear weapons production can pose. Even the challenge of cleaning up the results of four decades of nuclear weapons production from testing should be vast enough to tell us that testing must absolutely come to a complete stop around the world. Incredible resources will be needed to dispose of 2,700 tons of spent fuel, 10,500 hazardous substances, and 100 million gallons of high-level waste; to clean up 2.3 million acres of land; and to remediate 120 million square feet of buildings on 120 sites (Day 40-41). Four major tasks can be identified: to stabilize and maintain a large number of nuclear materials and facilities; to design, build, and operate a variety of treatment facilities to prepare waste for disposal and provide safe interim storage; to manage large amounts and varieties of wastes; and to work towards environmental restoration (Mosman 13). But nuclear weapons testing has had different effects all over the world. And the "not-in-my-backyard syndrome" has come to voice opinions everywhere.-- Nobo... ... Pie Chart Below : (Source : Mollison A/08) References Day Jr., Samuel. "The big lie.," Vol. 57, Progressive, 1 Jun 1993, pp. 40. Johnson, Douglas. "Atolls and atom bombs: France's colonial design.," Vol. 45, History Today, 1 Dec 1995, pp. 8. Mollison, Andrew. "Focus on Nuclear Testing." The Atlanta Constitution, 16 Aug 1995, pp. A/08. Mosman, Jan. "Ban nuclear tests.," Vol. 339, Economist, 4 May 1996, pp. 13. Ruben, Barbara, "How to really bomb a test.," Vol. 24, Environmental Action, 1 Jan 1993, pp. 8. Schull, William J. Effects of Atomic Radiation. (New York, NY: Free Press, 1995). Sternberg, Steve. "From war's holocaust, new radiation findings," The Atlanta Journal and Constitution, 20 Mar 1993, pp. F/01. Yamazaki, James N. Children of the Atomic Bomb. (Duke University Press, 1995).

Implement Marketing Strategies and Tactics Essay

Briefing stakeholders- Persons involved directly or indirectly with the organisation or project. BBQfun will be the leading outdoor-lifestyle retailer, catering to the growing need for furnishing new and renovated dwellings in the greater Brisbane area. Board of directors- BBQfun’s board of directors need to approve the plan, customers specific needs, prepare a report of high population in Greater Brisbane area, new homes and renovated homes growing from a base of 50,000 per year, low employment. Human resources staff-Human resources staff may need to adjustment demographic factors like – * Male and female population * Age segment that makes up 50% of the Brisbane new and renovated house markets, according to the chamber of commerce * High percentage of young professionals who work in the central Business district. * An average household income of over $130,000. Services marketing- Marketing based on relationship and value. BBQfun will position as a broad assortment, quality, unique outdoor –lifestyle retailer. Brisbane customers appreciate high quality and uniqueness will recognise the value and unique offerings of BBQfun. Manager- BBQfun’s manager looking for security in purchasing and house proud factor in outdoor lifestyle purchasing. Marketing and non-marketing personnel- The success of any marketing activities is equally shared between both external and internal customers group. BBQfun’s basic market need is for quality, fashionable and unique outdoor –lifestyle items that caters to the house- proud needs of our market. The success of the marketing plan of BBQfun’s many aspects are responsible for this like- advertising personnel, manager, public relations personnel, sales manager, sales team, staff, and supervisors. Objectives of the plan- * Increase sales from $15 millon per year to $20 million per year in the next three years. * Increase our loyalty customers list from 10,000 to 16,000. * Establish brand recognition in Brisbane so that at least two in three people recognise our brand in a random survey taken in 12 months’ time. * Continue increase gross profit margins. Roles and responsibilities-BBQfun’s responsibility is to provide customers with the most extensive assortment of quality outdoor-lifestyle products available in the market. Second, easy to manage long term repayment plans make unique, imported and high quality outdoor-lifestyle affordable to all. Performance measures- it is very important to know the performance measures of the BBQfun’s. There are four main steps for measuring – Customers- BBQfun’s excellent staff that is highly skilled and knowledgeable about outdoor lifestyles. High customer loyalty among repeat customers.BBQfun’s great retail space that is bright, functional and efficient. Customers can see the quality of the product as it is displayed in the store. Financial-BBQfun’s advertising budget is set at $250,000 for the year. Continue to finance the easy manage long term repayment. The imported products make up 33% of the assortment. Internal business process- BBQfun wants their products and service meet customer needs so BBQfun try to new dwelling population, shopping patterns requiring easy access and customer car parking counts. Learning and growth-BBQfun has created an outdoor- lifestyle range of retail products that are differentied and superior to competitors. BBQfun provide 3 year guarantee is unique in the market place. BBQfun want to grow their business in the commercial, suburban neighbourhood or urban retail district. BBQfun‘s will do direct mail and local advertising. BBQfun has 15-20 full time staff, plus casuals. Marketing strategies and the resources-A marketing strategy is the foundation of a marketing plan; it integrates an organisation’s marketing objectives, goals, policies and actions.BBQfun’s 3 types of marketing strategies- Defensive strategies- BBQfun’s mission is to provide customers with the most extensive assortment of quality products available in the market. BBQfun continue to finance the easy manage long term repayment plan for customers. Developing strategies-BBQfun’s developing strategy is increase sales from $15 million per year to $20 million pe r year in the next 3 years, increase loyalty customers list from 10,000 to 16,000. Attacking strategies- BBQfun’s customers are mostly aged between 20 to 50, making up 50% of the new and renovated dwelling market. Outdoor lifestyle stores have been very successful in stand alone, extensive car park access, close to new housing estates being established. By offering a superior service in range and uniqueness, BBQfun will excel relative to the competition and achieve goals. Resources -Elements that are utilised to assist the process like- human, information and communication technology, financial and physical. * Human resources relates to the people. BBQfun’s marketing plan and strategy related to the people because this is a outdoor lifestyle retailer company. BBQfun’s customers are male and female and high percentage of young professionals. * Financial- BBQfun’s advertising budget is $250,000 for the year. BBQfun will try to get articles about BBQfun into the BrisNews magazine. BrisNews magazine has seen a dramatic increase of sales immediately after the article was published. * ICT – For advertising purpose BBQfun is using local letter box, radio, and magazines. BBQfun‘s will do direct mail and local advertising, with coupon inserts in the BrisNews magazine likely to be the most successful of the campaigns. Communication and team building strategies- Effective communication is essential in any workplace and is essential for building or improving business and work relationships. Team building strategies are also essential in effectively running an organisation or team. BBQfun’s objective is to create customer awareness regarding their services offered, develop that customer base, and work toward building customer loyalty and referrals. The message of BBQfun is easy access outdoor-lifestyle products in Brisbane. This message will be communicated through a variety of methods like- direct mail. BBQfun will also use ads and inserts in Brizzy magazine. The 5Cs of effective team building are- Clear expectations-If we want to implement successful team building strategy then clear expectation is very important. In a team every person knows the role they are expected to play as well as the roles of other team members. Each and every member of the team needs to understand how and where they fit in the organisational structure. Channels of communication- Team building strategy cannot achieve without open channels of communication. It involves everyone like directors, managers, team leaders and team members. It helps to create working atmosphere and encourage to employees to discuss the problems amongst themselves. Conflict resolution-When a group of people working together then differences emerge into the open. By communication they try to solve the differences. If they can’t resolve their problems without assistance then implement mediation with an impartial third party and organise a workshop on this subject. Consequences- Make sure each team member feels responsible and accountable for team achievements. Understand the individual contribution and give them appreciation if they are doing well. In this way it encourages them for individual creativity. Celebrating achievements as a team- Every employee or team member plays an important role in the success or failure of an organisation. So need to celebrate achievements as a team. Marketing mix- BBQfun’s marketing mix is comprised of these following approaches to pricing, distribution, advertising and promotion and customer service. Strategies for monitoring marketing activities- The marketing plan require the monitoring of all marketing activities in order to analyse their performance. Implementation strategies for effective and accurate monitoring processes need to be considered and implemented. BBQfun’s each aspect of marketing plan should be monitored and evaluate. These aspects are important to achieve goal- Timeline, Resource, Costs, sales, contacts made relationship. BBQfun‘s single objective to position BBQ as the premier outdoor –lifestyle store in the greater Brisbane area within 5 years. BBQfun wants to create customer awareness regarding their service and work toward building customer loyalty and referrals. The direct mail campaign will be away to communicate directly with the consumer in this way BBQfun create a good relationship with customers. It is envisaged that new products will be developed on a regular basis in line with changes in customer taste which is targeted at every 12 months. By getting feedback from these firms then changes is possible in the product. Feedback, decision making process of customers is very important aspect for the development of the product. Local business owners are often part of an informal fraternal organisation where they support each other’s business. BBQfun recently become a member of the outdoor Lifestyle Association. BBQfun’s marketing manager is responsible for marketing activities and has the authority and responsibilities over all company activities that affect customer’s satisfaction. .

Marketing Mix Of Marketing Management - 1005 Words

Marketing Mix in marketing management is used to attract consumers and for sales promotion, using the four basic elements/components of the mix, namely, Product, Price, Place, and Promotion (four Ps). A combination and fair application of these marketing essentials is called Marketing Mix. The four Ps may sound simple but are the crucial marketing algorithm elements. The four Ps must work together and if any on the Ps fail, the entire marketing mix is in fault state. Assuming that if we have all four Ps, the marketing mix will work perfectly is not true. Each of the four Ps has to be targeted towards specific customer segment and be in sync with other four Ps at the same time. The first P is â€Å"Product† not only includes the product or service but also defines the variety, quality, design, packaging, design, brand, warranties, returns, or anything that is a part of your product purchase and adds value to the product. The second Price P is â€Å"Price† and just like the concept of product, price is not simply the retail price. Instead, the price boundary covers the retail price, product discounts, bonuses, promotions, payment period and credit terms. All these options tend to either reduce the price or make the payment process easier for the customer. Going forward to the next P, â€Å"Promotion† is required to publicize the product about which a marketer is trying to convey to its target audience. Promotion can be achieved through advertising, sales calls, personal selling, salesShow MoreRelatedThese Elements Are the Basic Elements of Marketing Plan and Overall It Is Known as 4ps. (Marketing Mix, 2009) These 4 Ps Are the Parameters Through Which the Marketing Management Can Control Internal and External Constraints of the Target Marketing.1115 Words   |  5 Pages$Marketing mix is a marketing tool that is uses by the organization to fulfill its target customers and achieve its organizational goals. Marketing tools are classified under these four encompassing categories. * product * Price * Place ( distribution) * Promotion These elements are the basic elements of marketing plan and overall it is known as 4P s. (marketing mix, 2009) These 4 Ps are the parameters through which the marketing management can control internal and external constraintsRead MoreProdut P Is Most Important in Marketing Mix1186 Words   |  5 Pages‘P’ IS ALWAYS THE SINGLE MOST IMPORTANT ELEMENT IN THE MARKETING MIX Definition of Marketing Mix According to  Philip Kotler  -  Marketing Mix  is the combination of four elements, called the 4Ps (product, Price, Promotion, and Place), that every company has the option of adding, subtracting, or modifying in order to create a desired marketing strategy Marketing Mix was first coined by Neil Bordon, the President of the American Marketing Association in 1953 and is referred to as the set of actionsRead MoreManagement Functions And Functions Of Management1381 Words   |  6 PagesThe term â€Å"Management† refers to the performance of some functions such as planning, organizing, controlling and directing by an individual or a group of individuals in order to achieve a common goal. Management is required when we work in group. Management functions cannot be performed in isolation . Management has been defined by a number of authors. Some of which are as follows: â€Å"Management is the art of getting things done through others† ---- Mary Parker Follett â€Å"Management is the coordinationRead MoreThe Relationship Between Strategic Planning And The Marketing Management Process759 Words   |  4 Pages MGMT 5302 – Marketing Analysis Final Exam Question #1 (6 points) Describe the relationship of strategic planning and the marketing management process. The strategic planning is a long look at the future or path of growth that the company wishes to go in. To achieve that growth or travel that path several objectives are needed to keep that company on the correct one, marketing management is a part of that process. If the market management is not adhering to the overall strategic plan of the companyRead MoreMarketing Mix : A Business Tool1726 Words   |  7 PagesThe term ‘Marketing mix’ is said to have first been used by Borden (1965). The term ‘Marketing mix’ was derived from the lone P (price) of microeconomic theory (Chong, 2003). The marketing mix is a business tool often used in marketing and by marketers. The marketing mix is important when trying to determine a product or brand s offer, and is often identified with the four P’s which are; price, place, promotion and product (McCarthy, 1964). Kent (1986) describes the four P’s as â€Å"the holy quadrupleRead MoreThe 4p Classification of the Marketing Mix Revisited1201 Words   |  5 PagesThe 4P s Classification of the Marketing Mix Revisited This article, addresses the prime classifications scheme in marketing, the 4P configuration of the marketing mix. The marketing discipline needs a strong classification of the marketing mix, not only to stimulate conceptual integration and purification of the discipline, but also for meaningful measurement of marketing mix efforts and their effects. Also, managers need a clear classification of all instruments at their disposal in orderRead MoreInternational Marketing Strategy1738 Words   |  7 PagesMARKETING ESSAY In affluent societies, one observes a growing fragmentation of markets, buyers requesting more and more products adapted to their specific needs. How can we reconcile this fact with the objectives of global marketing that emphasises a strategy of standardisation of products and brands across the entire world? Executive Summary: Companies developing a global marketing strategy must consider its impact and influence on the company. Crucial for development of global marketing strategyRead MoreCompany and Marketing Strategy: Partnering to Build Customer Relationships1465 Words   |  6 Pagesand how marketing works with its partners to create and deliver customer value 4. Describe the elements of a customer-driven marketing strategy and mix, and the forces that influence it 5. List the marketing management functions, including the elements of a marketing plan, and discuss the importance of measuring return on marketing investment Chapter Outline 1. Companywide Strategic Planning: Defining Marketing’s Role 2. Marketing Strategy and the Marketing Mix 3. Managing the Marketing Effort Read MoreWells Fargo771 Words   |  4 PagesApplications in Marketing 1104A-03 Marketing Management Project Type: Unit 5 Individual Project November 6, 2011 Wells Fargo is diversified financial service company providing investment banking, mortgage, consumer and commercial finance through more than 9,000 stores and 12,000 ATM’s across North America and internationally (Wells Fargo, 2011).Wells Fargo is the fourth largest bank in the U.S. by assets and the third largest bank Internationally (Marketing Mix, 2011). Wells FargoRead MoreThe Marketing Mix Of Borden1483 Words   |  6 PagesThe marketing mix was claimed to be introduced by Borden (1965) by himself and was suggested to him by Culliton (1948) as he described the action of a business decision-making as â€Å"mixer of ingredient†. The marketing mix is known to be a business tool to most, which needs to be taken under consideration in order for the business to be successful. The marketing mix was first originated from the single P, which was â€Å"Price† from the microeconomics theory (Chong 2003). Due to competiveness, new P’s were