Module Two Routes of Exposure
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Excretion and Storage of Ammonia by the Aquatic Larva of Sialis Lutaria (Neuroptera)
THE EXCRETION AND STORAGE OF AMMONIA BY THE AQUATIC LARVA OF SIALIS LUTARIA (NEUROPTERA) BY B. W. STADDON* Department of Zoology, University of Durham, King's College, Newcastle upon Tyne (Received 12 April 1954) INTRODUCTION Delaunay (1931), in a review of the invertebrates, showed that an excellent correla- tion existed between the nature of the major nitrogenous component of the excreta and the nature of the environment, aquatic or terrestrial, in which an animal lived. Ammonia was shown to predominate in the excreta of aquatic species, urea or uric acid in the excreta of semi-terrestrial or terrestrial species. Delaunay put forward the view that the synthesis by these terrestrial forms of more complex molecules from ammonia was essentially a detoxication mechanism necessitated by a restricted water supply. Although the insects are primarily a terrestrial group, representatives of a number of orders have become aquatic in one or more stages of their life histories. It is well known that those terrestrial species which have been examined, with the notable exception of blowfly larvae, excrete the bulk of their nitrogen in the form of uric acid (Wigglesworth, 1950). The possibility, however, that aquatic species might have reverted to ammonotelism does not seem to have been examined. Preliminary tests were carried out on the excreta of a variety of aquatic insects. In all cases ammonia was found to be the major nitrogenous excretory product. An investigation into various aspects of the metabolism, toxicity and excretion of ammonia was then undertaken on the aquatic larva of Siatis lutaria. It is the purpose of the present communication to present some observations on the excretion and storage of ammonia in this species. -
In Vitro Interactions of Epacadostat and Its Major Metabolites With
DMD Fast Forward. Published on March 10, 2017 as DOI: 10.1124/dmd.116.074609 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 74609 In vitro interactions of epacadostat and its major metabolites with human efflux and uptake transporters: Implications for pharmacokinetics and drug interactions Qiang Zhang, Yan Zhang, Jason Boer, Jack G. Shi, Peidi Hu, Sharon Diamond, and Downloaded from Swamy Yeleswaram Incyte Corporation, Wilmington, DE 19803 dmd.aspetjournals.org at ASPET Journals on September 29, 2021 1 DMD Fast Forward. Published on March 10, 2017 as DOI: 10.1124/dmd.116.074609 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 74609 Running title: Interactions of Epacadostat with Transporters Corresponding Author: Qiang Zhang, Ph.D. Incyte Corporation 1801 Augustine Cut-Off Wilmington, DE 19803 Downloaded from Email: [email protected] Phone: 302-498-5827 Fax: 302-425-2759 dmd.aspetjournals.org Number of Text Pages: 24 Number of Figures: 8 at ASPET Journals on September 29, 2021 Number of Tables: 6 Number of References: 24 The number of words of Abstract: 247 The number of words of Introduction: 655 The number of words of Discussion: 1487 Non-standard Abbreviations: EPAC, epacadostat; IDO1, indoleamine 2,3-dioxygenase 1; EHC, enterohepatic circulation; NME, new chemical entity; TEER, transepithelial electrical resistance; HBSS, Hank's Balanced Salt Solution; KO, knockout; CSA, cyclosporin A; IC50, half-maximal inhibitory concentration; ER, efflux ratio 2 DMD Fast Forward. Published on March 10, 2017 as DOI: 10.1124/dmd.116.074609 This article has not been copyedited and formatted. -
TOXICOLOGY and EXPOSURE GUIDELINES ______(For Assistance, Please Contact EHS at (402) 472-4925, Or Visit Our Web Site At
(Revised 1/03) TOXICOLOGY AND EXPOSURE GUIDELINES ______________________________________________________________________ (For assistance, please contact EHS at (402) 472-4925, or visit our web site at http://ehs.unl.edu/) "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy." This early observation concerning the toxicity of chemicals was made by Paracelsus (1493- 1541). The classic connotation of toxicology was "the science of poisons." Since that time, the science has expanded to encompass several disciplines. Toxicology is the study of the interaction between chemical agents and biological systems. While the subject of toxicology is quite complex, it is necessary to understand the basic concepts in order to make logical decisions concerning the protection of personnel from toxic injuries. Toxicity can be defined as the relative ability of a substance to cause adverse effects in living organisms. This "relative ability is dependent upon several conditions. As Paracelsus suggests, the quantity or the dose of the substance determines whether the effects of the chemical are toxic, nontoxic or beneficial. In addition to dose, other factors may also influence the toxicity of the compound such as the route of entry, duration and frequency of exposure, variations between different species (interspecies) and variations among members of the same species (intraspecies). To apply these principles to hazardous materials response, the routes by which chemicals enter the human body will be considered first. Knowledge of these routes will support the selection of personal protective equipment and the development of safety plans. The second section deals with dose-response relationships. -
Biotransformation: Basic Concepts (1)
Chapter 5 Absorption, Distribution, Metabolism, and Elimination of Toxics Biotransformation: Basic Concepts (1) • Renal excretion of chemicals Biotransformation: Basic Concepts (2) • Biological basis for xenobiotic metabolism: – To convert lipid-soluble, non-polar, non-excretable forms of chemicals to water-soluble, polar forms that are excretable in bile and urine. – The transformation process may take place as a result of the interaction of the toxic substance with enzymes found primarily in the cell endoplasmic reticulum, cytoplasm, and mitochondria. – The liver is the primary organ where biotransformation occurs. Biotransformation: Basic Concepts (3) Biotransformation: Basic Concepts (4) • Interaction with these enzymes may change the toxicant to either a less or a more toxic form. • Generally, biotransformation occurs in two phases. – Phase I involves catabolic reactions that break down the toxicant into various components. • Catabolic reactions include oxidation, reduction, and hydrolysis. – Oxidation occurs when a molecule combines with oxygen, loses hydrogen, or loses one or more electrons. – Reduction occurs when a molecule combines with hydrogen, loses oxygen, or gains one or more electrons. – Hydrolysis is the process in which a chemical compound is split into smaller molecules by reacting with water. • In most cases these reactions make the chemical less toxic, more water soluble, and easier to excrete. Biotransformation: Basic Concepts (5) – Phase II reactions involves the binding of molecules to either the original toxic molecule or the toxic molecule metabolite derived from the Phase I reactions. The final product is usually water soluble and, therefore, easier to excrete from the body. • Phase II reactions include glucuronidation, sulfation, acetylation, methylation, conjugation with glutathione, and conjugation with amino acids (such as glycine, taurine, and glutamic acid). -
Biopharmaceutical Properties of Patches Relevant for Transdermal Drug Absorption – Confounding Factors and In‐Vitro Testing
Biopharmaceutical Properties of Patches 16.06.2015 Relevant for Transdermal Drug Absorption Biopharmaceutical Properties of Patches Relevant for Transdermal Drug Absorption – Confounding Factors and In‐Vitro Testing Johannes Bartholomäus Pharmakreativ Consulting, Aachen Skin as Barrier to Transdermal Absorption And that’s from what Mother Nature did not design all the difficulties in transdermal drug skin as an absorption site. delivery arise. It‘s much more the opposite! Stratum corneum as lipophilic barrier June 16, 2015 J. Bartholomäus: Biopharmaceutical Properties of Patches 2 © Johannes Bartholomäus 1 Biopharmaceutical Properties of Patches 16.06.2015 Relevant for Transdermal Drug Absorption Definition TDDS by Guidelines . Transdermal drug delivery systems . Transdermal patch:** Flexible single‐ (TDDS):* A TDDS or transdermal dose preparation intended to be patch is a flexible pharmaceutical applied to the unbroken skin to preparation of varying size containing obtain a systemic delivery over an one or more active substance(s) to be extended period of time. applied on the intact skin for systemic . Transdermal patches consist of a availability. backing sheet supporting a reservoir . There are two main types of or a matrix containing the active transdermal patch systems substance(s) and on the top a depending on how the drug pressure‐sensitive adhesive, which substance is dispersed in other patch assures the adhesion of the components: preparation to the skin. – Matrix systems with drug release based on . The backing sheet is impermeable to the diffusion of drug substance. the active substance(s) and normally – Reservoir systems containing a specific liquid drug compartment and release is impermeable to water. controlled by a membrane. -
Pulmonary Delivery of Biological Drugs
pharmaceutics Review Pulmonary Delivery of Biological Drugs Wanling Liang 1,*, Harry W. Pan 1 , Driton Vllasaliu 2 and Jenny K. W. Lam 1 1 Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China; [email protected] (H.W.P.); [email protected] (J.K.W.L.) 2 School of Cancer and Pharmaceutical Sciences, King’s College London, 150 Stamford Street, London SE1 9NH, UK; [email protected] * Correspondence: [email protected]; Tel.: +852-3917-9024 Received: 15 September 2020; Accepted: 20 October 2020; Published: 26 October 2020 Abstract: In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by parenteral injection (with a very few exceptions). Pulmonary delivery is an attractive non-invasive alternative route of administration for local and systemic delivery of biologics with immense potential to treat various diseases, including diabetes, cystic fibrosis, respiratory viral infection and asthma, etc. The massive surface area and extensive vascularisation in the lungs enable rapid absorption and fast onset of action. Despite the benefits of pulmonary delivery, development of inhalable biological drug is a challenging task. There are various anatomical, physiological and immunological barriers that affect the therapeutic efficacy of inhaled formulations. This review assesses the characteristics of biological drugs and the barriers to pulmonary drug delivery. -
Absorption, Distribution, Metabolism, Excretion and Toxicology Dr
Draft Guidance Novel Foods Absorption, Distribution, Metabolism, Excretion and Toxicology Dr. Josef Schlatter Member of the Scientific Committee and EFSA’s WG on Novel Foods Stakeholder Meeting, 11 April 2016, Brussels Section 7 Absorption, Distribution, Metabolism, and Excretion (ADME) 2 7. ADME (1) Critical for the development of appropriate toxicity testing strategy including the selection of appropriate animal models. Important information for the interpretation of study results. Differences between experimental animals and humans. Consider tiered approach to toxicokinetic testing which are described in section 4.1 on « Toxicokinetics (ADME) » of the EFSA Guidance for food additive evaluations (EFSA ANS Panel, 2012). Negligible absorption may provide a scientific justification for not undertaking higher tiered toxicological studies. Single substances and simple mixtures should normally be tested according to the same principles as those applied to food additives. As a default, absorption of the Novel Food or its breakdown products should be assessed. 3 7. ADME (2) For food additives in the form of complex mixtures, the ANS Guidance states that «conventional metabolism and toxicokinetic studies may not be feasible for all components in the mixture, but should be provided for toxicologically relevant constituents. Toxicologically relevant constituents are generally considered to be the major components and those other components with known or demonstrable biological or toxicological activity, and should be determined on a case-by-case basis with a scientific justification and the rationale for their selection provided ». Whole foods should be tested like complex mixtures as stated in the ANS Guidance. 4 7. ADME (3) For Novel Foods, ADME assessment should also address nutritionally significant constituents where toxicokinetic data on these constituents are important considerations for the evaluation of the nutritional impact of the Novel Food. -
Pharmacology Part 2: Introduction to Pharmacokinetics
J of Nuclear Medicine Technology, first published online May 3, 2018 as doi:10.2967/jnmt.117.199638 PHARMACOLOGY PART 2: INTRODUCTION TO PHARMACOKINETICS. Geoffrey M Currie Faculty of Science, Charles Sturt University, Wagga Wagga, Australia. Regis University, Boston, USA. Correspondence: Geoff Currie Faculty of Science Locked Bag 588 Charles Sturt University Wagga Wagga 2678 Australia Telephone: 02 69332822 Facsimile: 02 69332588 Email: [email protected] Foot line: Introduction to Pharmacokinetics 1 Abstract Pharmacology principles provide key understanding that underpins the clinical and research roles of nuclear medicine practitioners. This article is the second in a series of articles that aims to enhance the understanding of pharmacological principles relevant to nuclear medicine. This article will build on the introductory concepts, terminology and principles of pharmacodynamics explored in the first article in the series. Specifically, this article will focus on the basic principles associated with pharmacokinetics. Article 3 will outline pharmacology relevant to pharmaceutical interventions and adjunctive medications employed in general nuclear medicine, the fourth pharmacology relevant to pharmaceutical interventions and adjunctive medications employed in nuclear cardiology, the fifth the pharmacology related to contrast media associated with computed tomography (CT) and magnetic resonance imaging (MRI), and the final article will address drugs in the emergency trolley. 2 Introduction As previously outlined (1), pharmacology is the scientific study of the action and effects of drugs on living systems and the interaction of drugs with living systems (1-7). For general purposes, pharmacology is divided into pharmacodynamics and pharmacokinetics (Figure 1). The principle of pharmacokinetics is captured by philosophy of Paracelsus (medieval alchemist); “only the dose makes a thing not a poison” (1,8,9). -
Isoxaflutole
ISOXAFLUTOLE First draft prepared by P.V. Shah 1 and Roland Alfred Solecki 2 1 Office of Pesticide Programs, Environmental Protection Agency, Washington, DC, United States of America (USA) 2 Federal Institute for Risk Assessment, Berlin, Germany Explanation ........................................................................................................................................... 393 Evaluation for acceptable daily intake .................................................................................................. 394 1. Biochemical aspects ............................................................................................................... 394 1.1 Absorption, distribution and excretion ............................................................................ 394 1.2 Biotransformation ........................................................................................................... 397 1.3 Dermal absorption ........................................................................................................... 399 2. Toxicological studies ............................................................................................................. 400 2.1 Acute toxicity .................................................................................................................. 400 (a) Oral administration .................................................................................................. 401 (b) Dermal application .................................................................................................. -
Clinical Pharmacology Elimination of Drugs
BRITISH MEDICAL JOURNAL VOLUME 282 7 MARCH 1981 809 Br Med J (Clin Res Ed): first published as 10.1136/bmj.282.6266.809 on 7 March 1981. Downloaded from Today's Treatment Clinical pharmacology Elimination of drugs H E BARBER, J C PETRIE This article outlines the principles ofdrug elimination, principally influenced by the lipid solubility of the drug. The more lipid by the liver and kidneys. Most elimination processes of drugs soluble the drug is, the more distribution into lipid compart- follow first-order elimination kinetics. In such processes a ments takes place and hence the larger is the Vd of the drug, defined and constant fraction of a drug-for example, half-is thus affecting its elimination. irreversibly eliminated in a constant time. The half-life time (t1) Drug clearance is also influenced by the rate of delivery of the in such first-order processes is the time taken for the concen- drug to the organs of elimination, principally the liver and tration of the drug to fall to half its previous value, regardless kidney, and by the capacity of the organs to eliminate the drug. of the initial concentration of the drug. Some drugs-for In clinical practice most drugs are swallowed and with some, example, ethyl alcohol-follow zero-order elimination kinetics. for example, propranolol, the bioavailability is low because only In these processes elimination of the drug occurs at a constant a fraction of the oral dose administered reaches the systemic rate, because the enzymes responsible for metabolism of drugs, circulation due to extensive presystemic or first-pass elimination and the active excretion processes particularly in the kidney, during absorption from the gut and passage through the liver. -
Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid
pharmaceutics Article Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid Yun Ju Kang 1, Chul Haeng Lee 2, Soo-Jin Park 3, Hye Suk Lee 4 , Min-Koo Choi 2,* and Im-Sook Song 1,5,* 1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea; [email protected] 2 College of Pharmacy, Dankook University, Cheonan 31116, Korea; [email protected] 3 College of Korean Medicine, Daegu Haany University, Daegu 38610, Korea; [email protected] 4 College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; [email protected] 5 BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, Korea * Correspondence: [email protected] (M.-K.C.); [email protected] (I.-S.S.); Tel.: +82-41-550-1438 (M.-K.C.); +82-53-950-8575 (I.-S.S.); Fax: +82-53-950-8557 (I.-S.S.) Abstract: We investigated the involvement of drug transporters in the pharmacokinetics of ros- marinic acid in rats as well as the transporter-mediated drug interaction potential of rosmarinic acid in HEK293 cells overexpressing clinically important solute carrier transporters and also in rats. Intravenously injected rosmarinic acid showed bi-exponential decay and unchanged rosmarinic acid was mainly eliminated by urinary excretion, suggesting the involvement of transporters in its renal excretion. Rosmarinic acid showed organic anion transporter (OAT)1-mediated active transport with a Km of 26.5 µM and a Vmax of 69.0 pmol/min in HEK293 cells overexpressing OAT1, and the plasma concentrations of rosmarinic acid were increased by the co-injection of probenecid because of decreased renal excretion due to OAT1 inhibition. -
Pharmaceutical Compounding and Dispensing Sample Chapter
Copyright Pharmaceutical Press www.pharmpress.com 6 Solutions Introduction and overview 101 Gargles and mouthwashes 105 General principles of solution preparation 103 Enemas and douches 105 Solubility 103 External solutions 105 Stability 103 Lotions 105 General method 103 Liniments 105 Oral solutions 104 Applications 105 Elixirs 104 Collodions 106 Linctuses 105 Worked examples 106 Syrups 105 Summary of essential principles relating to solutions 112 Mixtures 105 Packaging 112 Draughts 105 Discard dates 112 Spirits 105 Labelling 113 Paediatric drops 105 Introduction and overview Essentially a solution is a homogeneous liquid preparation that contains one or more dissolved med- Solutions are one of the oldest dosage forms used in the icaments. Since, by definition, active ingredients are treatment of patients and afford rapid and high dissolved within the vehicle, uniform doses by volume absorption of soluble medicinal products. Therefore, may be obtained without any need to shake the for- the compounding of solutions retains an important mulation. This is an advantage over some other for- place in therapeutics today. Owing to the simplicity mulation types (e.g. suspensions, see Chapter 7). and hence the speed of preparation of an ad hoc for- In general, water is chosen as the vehicle in which mulation, they are of particular use for individuals medicaments are dissolved, as it is non-toxic, non- who have difficulty in swallowing solid dosage forms irritant, tasteless, relatively cheap, and many drugs (for example paediatric, geriatric, intensive care and are water soluble. Problems may be encountered psychiatric patients), where compliance needs to be where active drugs are not particularly water soluble checked on administration (for example in prisons or or suffer from hydrolysis in aqueous solution.