DOCSLIB.ORG

Basic Course in Biopharmacy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Basic Course in Biopharmacy University of Szeged Basic Course in Biopharmacy Edited by: István Zupkó Ph.D. Authors: István Zupkó Ph.D. Eszter Ducza Ph.D. Árpád Márki Ph.D. Renáta Minorics Ph.D. Reviewed by: Gábor Halmos Ph.D. Szeged, 2015. This work is supported by the European Union, co-financed by the European Social Fund, within the framework of "Coordinated, practice-oriented, student-friendly modernization of biomedical education in three Hungarian universities (Pécs, Debrecen, Szeged), with focus on the strengthening of international competitiveness" TÁMOP-4.1.1.C-13/1/KONV-2014-0001 project. The curriculum can not be sold in any form! Contents 1. Basic concepts in pharmacology and biopharmacy. Routes of drug administration 1 1.1. Basic concepts in pharmacology and biopharmacy 1 1.2. Classification of routes of drug administration 2 1.2.1. Enteral drug administration 2 1.2.2. Parenteral drug administration 5 2. Receptors, signal transduction mechanisms 9 2.1. Introduction to pharmacological receptors 9 2.2. Signal transduction 10 2.3. G protein -coupled receptors ( GPCRs) 11 2.4. Ligand -gated ion channels 14 2.5. Receptors as enzymes 16 2.6. Nuclear hormone receptors and transcription factors 18 3. Dose –response relationships 21 3.1. General remarks 21 3.2. Concentration vs. response relationships in in vitro systems 22 3.3. Dose vs. response relationships in in vivo systems 26 4. Absorption and distribution of drugs and factors influencing this 30 4.1. Absorption of drugs 30 4.1.1. Main features of drug absorption 30 4.1.2. Absorption of drugs by passive diffusion 31 4.1.3. Absorption of drugs by active transport 33 4.1.4. Absorption of drugs by additional transport mechanisms 34 4.1.5. Factors influencing drug absorption 34 4.2. Distribution of drugs 37 4.2.1. General remarks 37 4.2.2. Volume of distribution 38 4.2.3. Binding to plasma proteins 39 4.2.4. Special drug distributions: the blood brain –barrier (BBB) and the placental barrier 39 5. The drug metabolism 42 5.1. The main features of the drug metabolism 42 5.2. Phase I of the drug metabolism 43 5.3. Phase II of the drug metabolism 48 5.4. Factors influencing the drug metabolism 50 6. Elimination, continuous intravenous infusion and multiple dosing regimen 53 6.1. Elimination 53 6.1.1. Renal excretion 53 6.1.2. Excretion by the liver 55 6.1.3. Pulmonary excretion 55 6.1.4. Salivary excretion 56 6.1.5. Excretion through the skin 56 6.1.6. Excretion into the breast milk 57 6.1.7. Clearance 57 6.2. Continuous intravenous infusion 58 6.2.1. Concept of plateau 59 6.2.2. Rate of infusion 59 6.2.3. Plateau fraction 61 6.2.4. Loading dose of the infusion 63 6.3. Multiple dosing regimen 63 6.3.1. Dosing interval ( τ) 65 6.3.2. Concept of plateau and minimum and peak plasma concentrations 66 6.3.3. Considerations during the application of a multiple dosing regimen 67 7. Compartmental models 70 7.1. One -compartment open model 71 7.1.1. One -compartment intravascular model 72 7.1.2. One -compartment extravascular model 74 7.2. Two -compartment open model 78 7.2.1. Two -compartment intravascular model 78 7.2.2. Two -compartment extravascular model 82 7.3. Effects of the ratio ka/ke on tmax and cmax 84 8. AUC, model-independent pharmacokinetics 87 8.1. Trapezoid method 87 8.2. Determination of AUC based on clearance 90 8.3. Model -independent pharmacokinetics 91 8.4. Application of model -independent calculations 95 8.4.1. Calculation of apparent volume of distribution at steady -state ( Vss ) 95 8.4.2. Calculation of the clearance ( Cl ) 96 8.4.3. Calculation of dosing rate 96 8.4.4. Calculation of bioavailability 97 9. Physiological and biological availability of drugs; bioequivalence 99 9.1. Introduction 99 9.2. Physiological availability 99 9.3. Biological availability (bioavailability) 100 9.3.1. Absolute bioavailability 100 9.3.2. Relative bioavailability 101 9.4. Special cases 102 9.5. Equivalence 102 9.5.1. Therapeutic alternatives 103 9.5.2. Pharmaceutical alternatives 103 9.5.3. Pharmaceutical (chemical) equivalence 103 9.5.4. Bioequivalence 104 9.5.5. Therapeutic equivalence 104 9.5.6. Generic preparations 104 9.6 Biosimilarity 105 10. Drug interactions 108 10.1. Relevance of drug interactions 108 10.2. Classification of drug interactions 108 10.3. Synergisms 110 10.3.1. Additive synergism 110 10.3.2. Potentiating synergism 110 10.4. Antagonisms 111 10.4.1. Chemical antagonism 111 10.4.2. Biological antagonism 112 10.4.3. Functional antagonism 112 10.4.4. Competitive antagonism 112 10.4.5. Non -competitive antagonism 114 10.4.6. Additional types of interactions 115 11. Factors influencing drug action and drug administration 118 11.1. Effects of age – Older patients 118 11.2. Effects of age – Paediatric patients 119 11.3. Sex differences 121 11.4. Body weight 122 11.5. Pregnancy 123 11.6. Genetic factors 124 11.7. Pathological factors 124 12. Non-linear pharmacokinetics and therapeutic drug monitoring 127 12.1. Non -linear pharmacokinetics 127 12.1.1. Relevance of non -linear pharmacokinetics 127 12.1.2. Capacity -limited metabolism 129 12.1.3. Estimation of Michaelis –Menten parameters ( Vmax and KM) 130 12.1.4. Additional possibilities for non -linear pharmacokinetics 132 12.2. Therapeutic drug monitoring (TDM) 133 12.2.1. Individualization of drug therapy 133 12.2.2. Theory of TDM 134 12.2.3. Practice of TDM 136 13. Adverse drug reactions 139 13.1. Classification of adverse drug reactions 139 13.2. Pharmacodynamic variation of genetic polymorphism 144 13.3 Pharmacokinetic variation of genetic polymorphism 145 14. Practical considerations 149 14.1. Important considerations of pharmacokinetic study design 150 14.1.1. Subjects 150 14.1.2. Types of study 150 14.1.3. Dosage form, route of administration 151 14.1.4. Accuracy in administration of the dose 151 14.1.5. Blood samples 152 14.1.6. Sample handling and timing 153 14.1.7. Curve fitting and statistical considerations 154 14.2. Pharmacokinetics and clinical situations 155 15. Suggested readings 159 1. Basic concepts in pharmacology and biopharmacy. Routes of drug administration 1.1. Basic concepts in pharmacology and biopharmacy One of the most important concepts is the pharmacon or drug. This is a synthetic or natural compound or substance which has the capacity to induce a characteristic action on a living organism. The term pharmacon is not limited to substances currently used in medicinal practice. It also involves all biologically active substances with no medical use (e.g. natural and synthetic toxins), all the agents withdrawn from medical use, and agents still under development. A pharmacon is not necessarily a chemically pure substance; it may be an extract from a natural source. The term active pharmaceutical ingredient (API) has a narrower meaning: it is the component in a medicinal preparation from which the therapeutic action is expected. There is no clear definition for the term poison. All pharmacons, including medically used agents, may exert detrimental action after their inappropriate application (e.g. in excessive doses). In a general sense, a poison is a substance which in a low dose has the capacity to cause a serious deterioration of a living organism. A drug usually induces a change in more than one physiological parameter, and therefore exerts more than one action. The main effect is the action for which the drug is administered, and all of the others are side-effects. Although the side-effects are generally unwanted or inconvenient consequences of the therapeutic dose of the given drug, a side-effect can sometimes be advantageous. For example, some of the agents used in psychiatry exert pronounced antihypertensive action, which can be utilized to maintain the optimum blood pressure. The relationship between the main and the side-effects can be relative: it depends on the aim of the drug administration. Atropine has a wide range of pharmacological actions and it could be administered to relax the smooth muscles, to decrease secretions or to constrict sphincters. In any given case, one of these is the main effect and all the others are side-effects. A toxic effect of a drug is always disadvantageous or harmful, and is exerted at a dose higher than the therapeutic dose. A toxic effect is therefore a consequence of an overdosage or intoxication. The site of action is that part of the living organism where the pharmacon exerts its actions. It can be an organ, a group of cells or a subcellular component (e.g. an organelle or even a molecule). Our current knowledge concerning the given drug usually determines the level at which the site of action is defined. For example, the site of action of digitalis glycosides is the 1 heart (as an organ), the cardiac muscle (a group of cells) or the Na/K-ATPase (a subcellular component). The mechanism of action refers to the sequence of reactions leading to the final pharmacological effect. An effect of a pharmacon can be local or general. A local effect is one where that the drug exerts its action only at the site of its application (e.g. antacids in the stomach, or eye drops). A general occurs when the drug is present in the blood circulation and can reach and influence all the possible sites of action in the body. A general effect can develop in two cases: • The drug is administered directly into the circulation (intravascular administration), or • the drug is administered outside the circulation (extravascular administration), but it can move from the site of application into the bloodstream.
Load more

Recommended publications
  • Pharmacokinetics of Pancreatic Polypeptide in Man
    Gut: first published as 10.1136/gut.19.10.907 on 1 October 1978. Downloaded from Gut, 1978, 19, 907-909 Pharmacokinetics of pancreatic polypeptide in man T. E. ADRIAN, G. R. GREENBERG, H. S. BESTERMAN, AND S. R. BLOOM From the Department ofMedicine, Royal Postgraduate Medical School, Hammersmith Hospital, London SUMMARY Pure bovine pancreatic polypeptide (PP) was infused into 23 healthy subjects at doses of 1, 3, and 5 pmol/kg/min over 60 minutes and plasma PP was measured by radioimmunoassay. During the infusions mean plasma levels of 203 + 34, 575 + 73, and 930 ± 48 pmol/l respectively were achieved. Mean disappearance half time on stopping the infusion was 6-9 + 0 3 min (mean + SEM). The metabolic clearance rate was 5-1 + 0-2 ml/kg/min (mean + SEM) and the apparent volume of distribution was calculated to be 51 ± 3 ml/kg (mean ± SEM). This study provides for the first time pharmacokinetic data for PP in man. Pancreatic polypeptide (PP) is a recently discovered syringe ram pump for a basal period of 30 minutes. hormonal 36 amino acid peptide localised in an BPP was then added to the infusion at nominal endocrine cell of the mammalian and avian pancreas doses of 1 (n = 6), 3 (n = 9), and 5 (n = 8) pmol/ (Kimmel et al., 1968; Lin and Chance, 1972). PP cir- kg/min. culates in plasma and levels rise substantially on the Blood samples were collected in chilled tubes with ingestion of a meal and remain raised for several 10 units heparin and 400 KIU aprotinin (Trasylol) hours (Adrian et al., 1976; Floyd et al., 1976; per ml, centrifuged, and the plasma frozen within 15 Schwartz et al., 1976).
    [Show full text]
  • Borax by the Forest Service from 2000 to 2004
    SERA TR-056-15-03c Sporax® and Cellu-Treat® (Selected Borate Salts) Human Health and Ecological Risk Assessment FINAL REPORT Submitted to: Dr. Harold Thistle USDA Forest Service Forest Health Technology Enterprise Team 180 Canfield St. Morgantown, WV 26505 Email: [email protected] USDA Forest Service Contract: AG-3187-C-12-0009 USDA Forest Order Number: AG-3187-D-15-0074 SERA Internal Task No. 56-15 Submitted by: Patrick R. Durkin Syracuse Environmental Research Associates, Inc. 8125 Solomon Seal Manlius, New York 13104 E-Mail: [email protected] Home Page: www.sera-inc.com October 17, 2016 Table of Contents LIST OF TABLES ......................................................................................................................... vi LIST OF FIGURES ....................................................................................................................... vi LIST OF APPENDICES ................................................................................................................ vi LIST OF ATTACHMENTS .......................................................................................................... vi ACRONYMS, ABBREVIATIONS, AND SYMBOLS .............................................................. viii COMMON UNIT CONVERSIONS AND ABBREVIATIONS ................................................... xi CONVERSION OF SCIENTIFIC NOTATION .......................................................................... xii EXECUTIVE SUMMARY ........................................................................................................
    [Show full text]
  • 7 X 11.5 Long Title.P65
    Cambridge University Press 978-0-521-51781-2 - Small Molecule Therapy for Genetic Disease Edited by Jess G. Thoene Index More information Index Abderhalden, Emil, 101 long-term therapy results, 147–149 absolute oral bioavailability, 37 side effects, 147 acquired copper deficiency, 202–203 antagonists, 46 active tubular secretion, 43 apomorphine, 12 acute hereditary tyrosinemia, 115 apoptosis, in cysteamine treatment, for adenosine triphosphate (ATP) nephropathic cystinosis, 103 ATP7A, 203 apparent first-order kinetics, 40–41 distal hereditary motor neuropathy, apparent volume of distribution, 39 206–207 argininosuccinate lyase (AL) deficiency, Menkes disease, 203 135 OHS, 206 argininosuccinate synthetase (AS) nephropathic cystinosis, 103 deficiency, 135 agonists, 46 AS deficiency. See argininosuccinate AKU. See alkaptonuria synthetase deficiency AL deficiency. See argininosuccinate lyase ATP. See adenosine triphosphate deficiency ATP7A, 203 ALA. See aminolevulinic acid distal hereditary motor neuropathy, alkaptonuria (AKU), 114, 118–121 206–207 cardiac involvement, 119–120 Menkes disease, 203 clinical presentation, 119 OHS, 206 arthritis as, 119 diagnosis, 121 basal ganglion diseases, 60 dietary therapies, 120 biotin therapy, 66 genetic factors, 121 inheritance factors, 63 HGA, 118–119 Bench-To-Bedside Research Program, HPPD inhibition, 124 25 incidence rates, 118–119 betaine, in homocystinuria treatment, nitisinone therapy, 125 176–179 future developments, 130 clinical evidence of, 176–177 side effects, 127 development, 176–177 tyrosine levels,
    [Show full text]
  • Viewed and Published Immediately Upon Acceptance Cited in Pubmed and Archived on Pubmed Central Yours — You Keep the Copyright
    Dynamic Medicine BioMed Central Research Open Access Modeling transitions in body composition: the approach to steady state for anthropometric measures and physiological functions in the Minnesota human starvation study James L Hargrove*†1, Grete Heinz†2 and Otto Heinz2 Address: 1Department of Foods and Nutrition, University of Georgia, Dawson Hall, Athens, GA, USA 30602 and 224710 Upper Trail Drive, Carmel, CA, USA 93923 Email: James L Hargrove* - [email protected]; Grete Heinz - [email protected]; Otto Heinz - [email protected] * Corresponding author †Equal contributors Published: 7 October 2008 Received: 17 July 2008 Accepted: 7 October 2008 Dynamic Medicine 2008, 7:16 doi:10.1186/1476-5918-7-16 This article is available from: http://www.dynamic-med.com/content/7/1/16 © 2008 Hargrove et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: This study evaluated whether the changes in several anthropometric and functional measures during caloric restriction combined with walking and treadmill exercise would fit a simple model of approach to steady state (a plateau) that can be solved using spreadsheet software (Microsoft Excel®). We hypothesized that transitions in waist girth and several body compartments would fit a simple exponential model that approaches a stable steady-state. Methods: The model (an equation) was applied to outcomes reported in the Minnesota starvation experiment using Microsoft Excel's Solver® function to derive rate parameters (k) and projected steady state values.
    [Show full text]
  • Variations in Intralipid Tolerance in Newborn Infants
    Pediatr. Res. 17: 478-481 (1983) Variations in Intralipid Tolerance in Newborn Infants ELIZABETH A. GRIFFIN,'^' M. HEATHER BRYAN,'^" AND AUBIE ANGEL The Research Institute of the Hospital for Sick Children and The Division of Endocrinology and Metabolism, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada Summary Intralipid tolerance test (IVLTT) in the calculation of an infusion rate to maintain the plasma Intralipid level at a predetermined Intravenous Intralipid tolerance tests (IVLTT) were done in 26 concentration was assessed. As Intralipid clearance at physiologic newborn infants of 26-40 wk gestational ages. The clearance triglyceride concentrations is considered to be exponential (17, (k2) constants ranged from 1.2-12.7 (%/min) after bolus injections 23), the formula of the plateau principle (10, 1 I) from pharma- given within 4.5 h (n = 12) or daily (n = 13). Significant variation cokinetics was applied to predict individual infusion rates. The (17-31%) occurred, similar to adults, and was unrelated to the plateau principal assumes that the plasma Intralipid concentration time or dose given. Eleven infants received continuous Intralipid is achieved when the rate of Intralipid infusion equals the rate of infusions for 10-24 h at a rate calculated to maintain a plasma Intralipid removal from the plasma compartment. Intralipid plateau concentration of 100 mg/dl. Nine infants did not exceed this optimal plasma level, although four could have toler- ated more Intralipid. Two infants exceeded the ideal plasma PATIENTS AND METHODS concentration (> 100 mg/dl). All infants achieved and maintained In order to assess the variability of the response of newborn plateaus within 5 h.
    [Show full text]
  • Rotenone Human Health and Ecological Risk Assessment FINAL REPORT
    SERA TR-052-11-03a Rotenone Human Health and Ecological Risk Assessment FINAL REPORT Submitted to: Paul Mistretta, COR USDA/Forest Service, Southern Region 1720 Peachtree RD, NW Atlanta, Georgia 30309 USDA Forest Service Contract: AG-3187-C-06-0010 USDA Forest Order Number: AG-43ZP-D-07-0010 SERA Internal Task No. 52-11 Submitted by: Patrick R. Durkin Syracuse Environmental Research Associates, Inc. 5100 Highbridge St., 42C Fayetteville, New York 13066-0950 Fax: (315) 637-0445 E-Mail: [email protected] Home Page: www.sera-inc.com September 17, 2008 Table of Contents ACRONYMS, ABBREVIATIONS, AND SYMBOLS ............................................................... vii COMMON UNIT CONVERSIONS AND ABBREVIATIONS................................................... ix CONVERSION OF SCIENTIFIC NOTATION ............................................................................ x EXECUTIVE SUMMARY ........................................................................................................... xi Overview.................................................................................................................................... xi Program Description ................................................................................................................. xii Human Health Risk Assessment..............................................................................................xiii Hazard Identification ...........................................................................................................xiii Exposure
    [Show full text]
  • Proposal for Defining the Relevance of Drug Accumulation Derived From
    BIOPHARMACEUTICS & DRUG DISPOSITION Biopharm. Drug Dispos. 36:93–103 (2015) Published online 21 January 2015 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/bdd.1923 Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms Christian Scheerans*, Roland Heinig, and Wolfgang Mueck Clinical Pharmacology, Bayer Pharma AG, Research Center, Wuppertal, Germany ABSTRACT: Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show ‘relevant’ drug accumulation at steady state (SS). This new requirement reveals three fundamental issues, which are discussed in the current work: first, measurement for the extent of drug accumulation (MEDA) predicted from single dose (SD) study data; second, its relationship with the percentage residual area under the plasma concentration–time curve τ τ ∞ (AUC) outside the dosing interval ( ) after SD administration, %AUC( - )SD; and third, the rationale τ ∞ ‘ ’ forathresholdof%AUC( - )SD that predicts relevant drug accumulation at SS. This work revealed that the accumulation ratio RA,AUC, derived from the ratio of the time-averaged plasma concentrations during τ at SS and after SD administration, respectively, is the ‘preferred’ MEDA for MR formulations. A τ ∞ causal relationship was derived between %AUC( - )SD and RA,AUC, which is valid for any drug (product) that shows (dose- and time-) linear pharmacokinetics regardless of the shape of the plasma concentration–time curve. Considering AUC thresholds from other guidelines together with the causal τ ∞ τ ∞ ≤ relationship between %AUC( - )SD and RA,AUC indicates that values of %AUC( - )SD 20%, resulting ≤ in RA,AUC 1.25, can be considered as leading to non-relevant drug accumulation.
    [Show full text]
  • Lecture 1 Pharmacodynamics =What Does the Drug Do to the Body ~Pharmacological Effects ~Physiological Effects
    LADME=what does the body do to the drug? = Pharmacokinetics Lecture 1 Pharmacodynamics =what does the drug do to the body ~Pharmacological effects ~Physiological effects Pharmacokinetics in your life What happens to a drug after its administration? A young child given an IM injection might ask : "How will that 'ouch' get from there to my sore throat"? LADME D 1. Liberation =releasing The answer to this question is the basis of 2. Absorption pharmacokinetics, i. e., how drugs move around the body A M and how quickly this movement occurs. E 3. Distribution During this semester many of the processes which control 4. Metabolism the absorption, distribution, metabolism, and excretion of drugs will be discussed. L 5. Excretion Getting drug from one site to another Disposition of drug in the body A D L IV= No A M E 1 one, two, and three compartment models Many of the processes involved in drug movement around the body are NOT saturated at normal therapeutic dose levels, making plasma concentration vs. time much simplified Parameters to be measured in 2 compartment model Rate for absorption Two compartment model often has wider application Common parameters of a blood time curve Therapeutic Range (window, index) All drugs are poisons Only proper administration determines whether a compound is beneficial or not The amount of drug administered and the resulting concentration in the body determines whether a drug is beneficial or detrimental The ideal range of drug concentrations within the body is referred as Therapeutic range (TR) or therapeutic window or therapeutic index (TI) 2 Therapeutic Range of a drug in Plasma Drug concentration vs.
    [Show full text]
  • 2-General Principles Final
    GENERAL PRINCIPLES (11) Subcommittee: Sitar, Daniel Chair [email protected] Cooke, William J. [email protected] Hein, David [email protected] Lam, Yui-Wing Francis, [email protected] Prozialeck, Walter [email protected] Eleven contact hours are recommended at the beginning of the course to provide the foundation for reinforcement and application of these principles throughout the course. Relevance USMLE topic Principles of therapeutics Pharmacodynamic and pharmacokinetic Pharmacokinetics; Mechanisms of drug processes – general principles action, structure-activity relationships; Concentration- and dose-effect relationships, types of agonists and antagonists and their actions; Mechanisms of drug adverse effects; Mechanisms of drug interactions; Regulatory issues; Signal transduction; Cell cycle/cell cycle regulation AAMC Medical School Objectives Topic A: Factors that make each patient Project Report X Patient Safety – unique Table 1 Topic B: Principles of clinically important pharmacokinetics Topic E: Rules and regulations that govern prescribing Topic F: Process and regulations governing drug discovery and development Topic H: How to find and use the most up-to-date information about drugs, biologics, and nutraceuticals Topic J: Adverse drug reactions Topic K: Drug-drug interactions 1. Introduction, Roots, and Definition of Terms a. Definition of Pharmacology The discipline that is concerned with understanding the interactions of chemical substances with living systems, and the application of this understanding to the practice of medicine. b. Relation to Other Disciplines i. Basis in Chemistry, Physiology, Biochemistry, Immunology and Molecular Biology ii. A foundation of medical practice, including historic perspective c. Key Terms and Concepts i. Drug - a substance that acts, often by interaction with regulatorymolecules, to stimulate or inhibit physiologic processes.
    [Show full text]
  • Dynamic Medicine Biomed Central
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Dynamic Medicine BioMed Central Research Open Access Modeling transitions in body composition: the approach to steady state for anthropometric measures and physiological functions in the Minnesota human starvation study James L Hargrove*†1, Grete Heinz†2 and Otto Heinz2 Address: 1Department of Foods and Nutrition, University of Georgia, Dawson Hall, Athens, GA, USA 30602 and 224710 Upper Trail Drive, Carmel, CA, USA 93923 Email: James L Hargrove* - [email protected]; Grete Heinz - [email protected]; Otto Heinz - [email protected] * Corresponding author †Equal contributors Published: 7 October 2008 Received: 17 July 2008 Accepted: 7 October 2008 Dynamic Medicine 2008, 7:16 doi:10.1186/1476-5918-7-16 This article is available from: http://www.dynamic-med.com/content/7/1/16 © 2008 Hargrove et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: This study evaluated whether the changes in several anthropometric and functional measures during caloric restriction combined with walking and treadmill exercise would fit a simple model of approach to steady state (a plateau) that can be solved using spreadsheet software (Microsoft Excel®). We hypothesized that transitions in waist girth and several body compartments would fit a simple exponential model that approaches a stable steady-state. Methods: The model (an equation) was applied to outcomes reported in the Minnesota starvation experiment using Microsoft Excel's Solver® function to derive rate parameters (k) and projected steady state values.
    [Show full text]
  • Pharmacology/Therapeutics I Block 1 Lectures – 2013-14
    Pharmacology/Therapeutics I Block 1 Lectures – 2013‐14 1. Introduction to Pharmacology – Clipstone 2. Principles of Pharmacology – Fareed 3. Drug Absorption & Distribution – Byron 4. Drug Elimination & Multiple Dosing – Byron 5. Clinical Pharmacokinetics – Quinn 6. Drug Metabolism – Marchese 7. Pharmacogenomics – Marchese 8. Drug Toxicity – Marchese 9. Pharmacodynamics I – Battaglia 10. Pharmacodynamics II – Battaglia 11. Drug Discovery & Clinical Trials – To Be Posted Later Pharmacology & Therapeutics Introduction August 5th, 2013 N.A. Clipstone, Ph.D. PHARMACOLOGY & THERAPEUTICS COURSE INTRODUCTION I. INTRODUCTION Overview (i) The word Pharmacology is originally derived from the Greek: pharmakon –meaning drug and logos-meaning knowledge. (ii) Pharmacology can be defined as “the study of the effects of drugs on the function of living organisms”. In a broader sense, Pharmacology deals with the actions, mechanism of action, clinical uses, adverse effects and the fate of drugs in the body. (iii) Drugs are defined as chemical substances, other than nutrients or essential dietary ingredients, that when administered to a living organism result in a distinct biological outcome. (iv) Drugs maybe purified chemicals, synthetic organic chemicals, substances purified from either plant or animal products or recombinant proteins generated by genetic engineering. (v) In order for a drug to be effective it has to be administered by an appropriate route (i.e. oral, intravenous or intramuscular etc) capable of achieving a sufficiently high enough concentration within its target tissue(s) in a chemical form that allows it to interact with its biological target to achieve its desired effect. (vi) The factors that determine the ability of a drug to reach its target tissue and achieve its desired therapeutic effect are determined by its inherent Pharmacokinetic and Pharmacodynamic properties.
    [Show full text]
  • Pharmacology/Therapeutics I Block I Lectures
    Pharmacology/Therapeutics I Block I lectures 2012‐2013 1 Introduction – Clipstone/Hoppensteadt 2. Principles of Pharmacology ‐ Fareed 3 Drug Absorption Distribution ‐ Byron 4. Drug Elimination & Multiple Dosing ‐ Byron 5 Drug Metabolism – Marchese 6. Clinical Pharmacokinetics – Quinn 7. Pharmacodynamics I – Battaglia (to be posted later) 8. Pharmacodynamics II – Battaglia (to be posted later) 9. Pharmacogenomics – Marchese 10. Drug Toxicity – Marchese 11. Drug Discovery and Clinical Trials – Lee (to be posted later) Pharmacology & Therapeutics Introduction August 6th, 2012 N.A. Clipstone, Ph.D. PHARMACOLOGY & THERAPEUTICS COURSE INTRODUCTION I. INTRODUCTION Overview (i) The word Pharmacology is originally derived from the Greek: pharmakon –meaning drug and logos-meaning knowledge. (ii) Pharmacology can be defined as “the study of the effects of drugs on the function of living organisms”. In a broader sense, Pharmacology deals with the actions, mechanism of action, clinical uses, adverse effects and the fate of drugs in the body. (iii) Drugs are defined as chemical substances, other than nutrients or essential dietary ingredients, that when administered to a living organism result in a distinct biological outcome. (iv) Drugs maybe purified chemicals, synthetic organic chemicals, substances purified from either plant or animal products or recombinant proteins generated by genetic engineering. (v) In order for a drug to be effective it has to be administered by an appropriate route (i.e. oral, intravenous or intramuscular etc) capable of achieving a sufficiently high enough concentration within its target tissue(s) in a chemical form that allows it to interact with its biological target to achieve its desired effect. (vi) The factors that determine the ability of a drug to reach its target tissue and achieve its desired therapeutic effect are determined by its inherent Pharmacokinetic and Pharmacodynamic properties.
    [Show full text]