DOCSLIB.ORG

Pharmacokinetics and Human Tissue Penetration of Flurithromycin G

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pharmacokinetics and Human Tissue Penetration of Flurithromycin G ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 1988, p. 1875-1878 Vol. 32, No. 12 0066-4804/88/121875-04$02.00/0 Copyright © 1988, American Society for Microbiology Pharmacokinetics and Human Tissue Penetration of Flurithromycin G. BENONI,1* L. CUZZOLIN,l R. LEONE,' U. CONSOLO,2 G. FERRONATO,2 C. BERTRAND,3 V. PUCHETTI,3 AND M. E. FRACASSO1 Institute ofPharmacology,1 Surgical Clinic-Thoracic Surgery Unit,3 and Institute ofDental Medicine,2 University of Verona, 37134 Verona, Italy Received 13 May 1988/Accepted 21 September 1988 The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to a favorable therapeutic result. Flurithromycin (Pierrel S.p.A.), an (8S)-8-fluoroerythro- omy were studied. Informed consent was obtained from mycin, shows the same spectrum of antimicrobial activity as each patient. The patients had normal renal and hepatic does erythromycin and the same activity in vitro (4, 9). function, and none had received any antibiotics in the month Preliminary information on the kinetics of this drug in before the surgery. healthy volunteers suggests that flurithromycin has good These patients received a total of seven doses of 500 mg of bioavailability and attains suitable levels in serum (1). We flurithromycin at 8-h intervals. Blood samples were taken investigated the pharmacokinetics of flurithromycin after after one administration of a 500-mg dose and on the morning single and multiple doses and studied its penetration into of day 3 after the last dose. Blood samples were taken at 0, bone, soft tissue, lung, and pericardial fluid in surgery 0.5, 1, 2, 4, 6, and 7 h after drug administration. patients. Since the antibacterial activity of antibiotics in vivo and 7 cannot be predicted only from activity in vitro and free Lung tissue samples were collected at 1.5, 2.6, 4, 5, concentrations in serum, we studied the relationship be- h after drug administration and homogenized in an equal tween free flurithromycin concentrations in serum and levels volume of 0.1 M phosphate buffer (pH 8). The homogenates in interstitial fluid, calculated from total drug content in were centrifugated at 1,200 x g in a refrigerated centrifuge, tissue, and consequently the difference in drug penetration and the supernatants were immediately assayed. Pericardial into different tissues. fluid samples were collected at 1.5, 3.5, 3.8, 5.7, and 7 h during surgery and assayed in toto. Drug assay and kinetic model. All samples were assayed MATERIALS AND METHODS within 2 h of collection by a microbiological method, using Bone and soft tissue. Twelve male patients (20 to 31 years antibiotic medium 1 and Micrococcus luteus ATCC 9341 as old and weighing 58 to 72 kg) undergoing maxillofacial the indicator organism. Serum, tissue, and pericardial fluid surgery were included in the study. Each patient had a samples were assayed against standards prepared in serum, normal clinical examination, normal hematological findings, tissue, and fluid samples of subjects who had received no and normal renal and liver function tests. None of the antibiotic therapy. The limit of detection of the assay was subjects took other drugs or antibiotics at least 2 weeks 0.03 ,g/ml. The assay had a coefficient of variation of 6.5% before the surgery. Informed consent was obtained from and a mean relative error of 8%. Assays of hemoglobin in each patient before flurithromycin administration. Each pa- tissues and correction of flurithromycin concentrations for tient received a total of 10 doses of 500 mg of antibiotic at 8-h blood contamination were performed according to Kroening intervals. Blood samples were taken after one administration et al. (8). of 500 mg of flurithromycin and on the morning of day 4 after The sampling period was long enough to allow drug levels the last (10th) dose, during surgery. Blood samples were in serum after one dose to approach zero or at least low taken at 0, 0.25, 0.5, 1, 1.5, 3, and 8 h after drug adminis- values. Free concentrations in serum were calculated from tration. the total levels in serum by correction for protein binding, Bone and soft tissue samples, obtained from each patient which amounted to 70% (G. Bonardi, unpublished data) for at 1, 1.5, 2, and 3 h after drug administration, were pulver- flurithromycin. Binding of flurithromycin to serum protein is ized with a Spex freezer mill and diluted 1:3 in 0.1 M independent of drug concentration. phosphate buffer (pH 8) before assay. A model was assumed in which free antibiotic can diffuse Lung tissue and pericardial fluid. Nine male patients (56 to passively from plasma to interstitial fluid. Both the volume 68 years old and weighing 78 to 47 kg) undergoing thoracot- of interstitial fluid (as a fraction of total tissue volume) and the binding to other tissue constituents are unknown. In the * Corresponding author. model used by us, the following equations hold: 1875 1876 BENONI ET AL. ANTIMICROB. AGENTS CHEMOTHER. I *Stde 10th dese (during surgery) =eg/=I , -. I. Om sa« i a bm 0 4 TTii 8 mrs FIG. 1. Concentration-time curves after single and multiple doses (500 mg every 8 h) of flurithromycin in patients undergoing maxillofacial surgery. Symbols: 0, total concentration in serum; 0, free concentration in serum; *, total content in bone tissue; A, total content in soft tissue. dCildt = DaCp - DaCi (1) pericardial fluid, elimination of the drug, and the relationship in which C1 is the concentration in interstitial fluid, Cp is the between drug levels in blood and tissues. After correction concentration in plasma (nonprotein bound), D is the diffu- for protein binding, the free concentrations in serum were sion coefficient, and a is the area-of-diffusion boundary. calculated. Fig. 1 and 2 show the curves of the total free Integration leads to concentrations in serum after single and multiple doses of flurithromycin and drug content in lung, bone, soft tissue, and pericardial fluid. These curves are based on the means of Ci = Da(J Cpdt - Cidt) (2) the results of two values at each time point; standard deviations were not calculated. in which Cdt is the area under the concentration-time curve The AUC from 0 to 7 h for lung samples was 23.4 ,ug h/g, (AUC) when Ci returns to zero after the first dose. Equation and the AUCs from 0 to 3 h for bone and soft tissue samples 1 leads to were 2.4 and 1.93 ,ug- h/g, respectively. The ratios of flurithromycin AUC from 0 to T in tissues to that in serum C1dt= J Cpdt (3) were 2.15 for lung, 0.58 for bone, and 0.46 for soft tissue. Moreover, the AUC,,s in tissue (in micrograms hour per gram) were 54.8 for lung, 31 for bone, and 7.0 for soft tissue. The relationship between tissue content and concentrations The ratios (R) of AUCo. in tissues to that in serum were 8.3 in interstitial fluid and other tissue components is expressed for lung, 3.6 for bone, and 0.8 for soft tissue. by Concentrations in the interstitial fluid at individual time Ct = fiCi + (1 D)Cr (4) points were calculated by dividing through R total content in in which Ct is total tissue content, f; is the volume fraction of tissues. Figure 3 shows the curves of the free antibiotic interstitial fluid, and Cr is the mean concentration in other concentrations in serum and the calculated concentrations in tissue components. Combination of equations 3 and 4 leads interstitial fluid. The calculated contents in the interstitial to AUC,/AUCp = (R -f1)1(1 - f]), in which R = AUCt/ fluid of bone and lung tissues were similar to the free AUCp. In these equations, the subscripts r, p, i, and t refer concentrations in serum, whereas concentrations in soft to measurements in other tissue components, in plasma, in tissue were very different. interstitial fluid, and in tissue, respectively. The pharmacokinetic parameters (mean and standard de- The predicted accumulation factor (Rp) was calculated by viation) for each group after the first and last doses of dividing 1 by the quantity (1 - e-T), in which ,B was flurithromycin are presented in Table 1. The mean residence determined from the first dose and T was the dose interval. times were 10.2 h for group 1 and 8.3 h for group 2. The ratio The observed accumulation factor (Ro) was determined by of the AUC during a dose interval to the AUC for the first the ratio of the AUC from 0 h to infinity (AUC_OO) for the last dose averaged 0.25 for group 1 and 0.67 for group 2.
Load more

Recommended publications
  • Compositions and Formulations Based on Swellable Matrices for Sustained Release of Poorly Soluble Drugs Such As Clarithromycin
    (19) & (11) EP 2 283 824 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 16.02.2011 Bulletin 2011/07 A61K 9/20 (2006.01) A61K 31/00 (2006.01) (21) Application number: 09166824.4 (22) Date of filing: 30.07.2009 (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • Camponeschi, Claudio HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL 00040, Pomezia (IT) PT RO SE SI SK SM TR • Colombo, Paolo Designated Extension States: 43100, Parma (IT) AL BA RS (74) Representative: Palladino, Saverio Massimo et al (71) Applicants: Notarbartolo & Gervasi S.p.A. • Special Products Line S.p.A. Corso di Porta Vittoria, 9 00040 Pomezia (IT) 20122 Milano (IT) • So. Se. Pharm S.r.l. 00040 Pomezia (IT) (54) Compositions and formulations based on swellable matrices for sustained release of poorly soluble drugs such as clarithromycin (57) The present invention concerns the discovery uct, capable to provide a quasi-constant prolonged re- of a new formulation for oral drug sustained release prod- lease of poorly soluble drugs whose solubility depends on the pH. EP 2 283 824 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 283 824 A1 Description FIELD OF THE INVENTION 5 [0001] The present invention concerns the discovery of new compositions and formulations for oral drug modified release products, capable to provide a sustained release of poorly soluble drugs whose solubility depends on the pH. BACKGROUND OF THE INVENTION 10 [0002] New drug dosage forms facilitating the human therapeutic practice are needed for making efficient the treatment of several diseases.
    [Show full text]
  • WHO Report on Surveillance of Antibiotic Consumption: 2016-2018 Early Implementation ISBN 978-92-4-151488-0 © World Health Organization 2018 Some Rights Reserved
    WHO Report on Surveillance of Antibiotic Consumption 2016-2018 Early implementation WHO Report on Surveillance of Antibiotic Consumption 2016 - 2018 Early implementation WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation ISBN 978-92-4-151488-0 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons. org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non- commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Surveillance of Antimicrobial Consumption in Europe 2013-2014 SURVEILLANCE REPORT
    SURVEILLANCE REPORT SURVEILLANCE REPORT Surveillance of antimicrobial consumption in Europe in Europe consumption of antimicrobial Surveillance Surveillance of antimicrobial consumption in Europe 2013-2014 2012 www.ecdc.europa.eu ECDC SURVEILLANCE REPORT Surveillance of antimicrobial consumption in Europe 2013–2014 This report of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Klaus Weist. Contributing authors Klaus Weist, Arno Muller, Ana Hoxha, Vera Vlahović-Palčevski, Christelle Elias, Dominique Monnet and Ole Heuer. Data analysis: Klaus Weist, Arno Muller and Ana Hoxha. Acknowledgements The authors would like to thank the ESAC-Net Disease Network Coordination Committee members (Marcel Bruch, Philippe Cavalié, Herman Goossens, Jenny Hellman, Susan Hopkins, Stephanie Natsch, Anna Olczak-Pienkowska, Ajay Oza, Arjana Tambić Andrasevic, Peter Zarb) and observers (Jane Robertson, Arno Muller, Mike Sharland, Theo Verheij) for providing valuable comments and scientific advice during the production of the report. All ESAC-Net participants and National Coordinators are acknowledged for providing data and valuable comments on this report. The authors also acknowledge Gaetan Guyodo, Catalin Albu and Anna Renau-Rosell for managing the data and providing technical support to the participating countries. Suggested citation: European Centre for Disease Prevention and Control. Surveillance of antimicrobial consumption in Europe, 2013‒2014. Stockholm: ECDC; 2018. Stockholm, May 2018 ISBN 978-92-9498-187-5 ISSN 2315-0955
    [Show full text]
  • Development of Novel Antibiotic Classes
    60 years ago… The changes in antibiotic research as shown by patent publications Development of Novel Antibiotic Classes 1930 1940 1950 1960 1970 1980 1990 2000 2003 Daptomycin 1999 Linezolid 1962 Quinolones 1962 Streptogramins 1958 Glycopeptides 1952 Macrolides 1950 Aminoglycosides 1949 Chloramphenicol 1949 Tetracyclines 1940 Beta-Lactams 1936 Sulfonamides Harald Labischinski Products in the Pipeline Product Class Main Segment Status ABT 492 Quinolone Community Ph II DK507k Quinolone Community Ph I Daptomycin Lipopeptide Hospital Reg. Oritavancin Glycopeptide Hospital Ph III Dalbavancin Glycopeptide Hospital Ph III Tigecycline Glycylcycline Hospital Ph III AR 100 Trimethoprime Hospital Ph II BAL 9141 Cephalosporin Hospital Ph II BB-83698 PDF-inhibitor Community Ph I CS-023 Carbapenem Hospital Ph II Until 2008 very few antibiotics will reach the market ! Harald Labischinski 60 years ago… 1942 Gardner and Chain discover a substance with antibacterial activity, produced by a strain of Proactinomyces (later Streptomyces gardneri), which they name proactinomycin A. Macrolide structure • Macrolides are lipophilic molecules with a characteristic central lactone ring bearing 12 to 17 atoms, few if any double bonds and no nitrogen athoms (until the advent of the azalides). • Several amino and/or neutral sugars can bind to the lactone ring. MACROLIDE ANTIBIOTICS 12-membered-ring 14-membered-ring 15-membered-ring 16-membered-ring 17-membered-ring Methymycin Natural Semi-synthetic Azithromycin Natural Semi-synthetic Lankacidin Neomethymycin compounds derivatives compounds derivatives complex YC-17 Litorin Erythromycin A to F Roxithromycin Josamycin Rokitamycin Oleandomycin Dirithromycin Kitasamycin Miokamycin Sporeamicin Flurithromycin Spiramycin Clarithromycin Midecamycin • The macrolides narrow the entrance of the tunnel through which the nascent polypeptide chain is extruded from the ribosome.
    [Show full text]
  • Summary Report on Antimicrobials Dispensed in Public Hospitals
    Summary Report on Antimicrobials Dispensed in Public Hospitals Year 2014 - 2016 Infection Control Branch Centre for Health Protection Department of Health October 2019 (Version as at 08 October 2019) Summary Report on Antimicrobial Dispensed CONTENTS in Public Hospitals (2014 - 2016) Contents Executive Summary i 1 Introduction 1 2 Background 1 2.1 Healthcare system of Hong Kong ......................... 2 3 Data Sources and Methodology 2 3.1 Data sources .................................... 2 3.2 Methodology ................................... 3 3.3 Antimicrobial names ............................... 4 4 Results 5 4.1 Overall annual dispensed quantities and percentage changes in all HA services . 5 4.1.1 Five most dispensed antimicrobial groups in all HA services . 5 4.1.2 Ten most dispensed antimicrobials in all HA services . 6 4.2 Overall annual dispensed quantities and percentage changes in HA non-inpatient service ....................................... 8 4.2.1 Five most dispensed antimicrobial groups in HA non-inpatient service . 10 4.2.2 Ten most dispensed antimicrobials in HA non-inpatient service . 10 4.2.3 Antimicrobial dispensed in HA non-inpatient service, stratified by service type ................................ 11 4.3 Overall annual dispensed quantities and percentage changes in HA inpatient service ....................................... 12 4.3.1 Five most dispensed antimicrobial groups in HA inpatient service . 13 4.3.2 Ten most dispensed antimicrobials in HA inpatient service . 14 4.3.3 Ten most dispensed antimicrobials in HA inpatient service, stratified by specialty ................................. 15 4.4 Overall annual dispensed quantities and percentage change of locally-important broad-spectrum antimicrobials in all HA services . 16 4.4.1 Locally-important broad-spectrum antimicrobial dispensed in HA inpatient service, stratified by specialty .
    [Show full text]
  • Application of Different Analytical Techniques and Microbiological
    International Scholarly Research Network ISRN Analytical Chemistry Volume 2012, Article ID 859473, 17 pages doi:10.5402/2012/859473 Review Article Application of Different Analytical Techniques and Microbiological Assays for the Analysis of Macrolide Antibiotics from Pharmaceutical Dosage Forms and Biological Matrices Lantider Kassaye Bekele and Getachew Genete Gebeyehu Food and Drug quality Control Laboratory, Food, Medicine and Health Care Administration and Control Authority of Ethiopia, Addis Ababa 5681, Ethiopia Correspondence should be addressed to Lantider Kassaye Bekele, [email protected] Received 7 March 2012; Accepted 2 May 2012 Academic Editors: I. Lavilla and I. Zhukov Copyright © 2012 L. K. Bekele and G. G. Gebeyehu. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars may be attached. They are produced by Streptomyces species and used primarily against gram-positive bacteria. The determination of antibiotics, including macrolides, is mainly carried out by microbiological assays. However, microbiological assays tended to lack specificity. And hence to overcome this problem, lots of chemical and instrumental methods have been developed to determine macrolides separately as well as simultaneously. Different chromatographic, spectrophotometric, and electrochemical methods used for the determination of macrolides have been reviewed in this paper. 1. Introduction as the increase in the resistance of gram-positive and gram negative strains, slow bactericidal action, associated gas- Antibiotics are substances produced by microorganisms, trointestinal disturbance, allergic reactions, and hepatotoxic which suppress the growth of or kill other microorganisms effects [2, 3].
    [Show full text]
  • Common Study Protocol for Observational Database Studies WP5 – Analytic Database Studies
    Arrhythmogenic potential of drugs FP7-HEALTH-241679 http://www.aritmo-project.org/ Common Study Protocol for Observational Database Studies WP5 – Analytic Database Studies V 1.3 Draft Lead beneficiary: EMC Date: 03/01/2010 Nature: Report Dissemination level: D5.2 Report on Common Study Protocol for Observational Database Studies WP5: Conduct of Additional Observational Security: Studies. Author(s): Gianluca Trifiro’ (EMC), Giampiero Version: v1.1– 2/85 Mazzaglia (F-SIMG) Draft TABLE OF CONTENTS DOCUMENT INFOOMATION AND HISTORY ...........................................................................4 DEFINITIONS .................................................... ERRORE. IL SEGNALIBRO NON È DEFINITO. ABBREVIATIONS ......................................................................................................................6 1. BACKGROUND .................................................................................................................7 2. STUDY OBJECTIVES................................ ERRORE. IL SEGNALIBRO NON È DEFINITO. 3. METHODS ..........................................................................................................................8 3.1.STUDY DESIGN ....................................................................................................................8 3.2.DATA SOURCES ..................................................................................................................9 3.2.1. IPCI Database .....................................................................................................9
    [Show full text]
  • Point Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in European Acute Care Hospitals
    TECHNICAL DOCUMENT Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals Protocol version 5.3 www.ecdc.europa.eu ECDC TECHNICAL DOCUMENT Point prevalence survey of healthcare- associated infections and antimicrobial use in European acute care hospitals Protocol version 5.3, ECDC PPS 2016–2017 Suggested citation: European Centre for Disease Prevention and Control. Point prevalence survey of healthcare- associated infections and antimicrobial use in European acute care hospitals – protocol version 5.3. Stockholm: ECDC; 2016. Stockholm, October 2016 ISBN 978-92-9193-993-0 doi 10.2900/374985 TQ-04-16-903-EN-N © European Centre for Disease Prevention and Control, 2016 Reproduction is authorised, provided the source is acknowledged. ii TECHNICAL DOCUMENT PPS of HAIs and antimicrobial use in European acute care hospitals – protocol version 5.3 Contents Abbreviations ............................................................................................................................................... vi Background and changes to the protocol .......................................................................................................... 1 Objectives ..................................................................................................................................................... 3 Inclusion/exclusion criteria .............................................................................................................................. 4 Hospitals .................................................................................................................................................
    [Show full text]
  • Statistical Analysis Plan / Data Specifications the Risk of Acute Liver Injury Associated with the Use of Antibiotics. a Replica
    WP6 validation on methods involving an extended audience Statistical analysis plan / data specifications The risk of acute liver injury associated with the use of antibiotics. A replication study in the Utrecht Patient Oriented Database Version: July 11, 2013 Authors: Renate Udo, Marie L De Bruin Reviewers: Work package 6 members (David Irvine, Stephany Tcherny-Lessenot) 1 1. Context The study described in this protocol is performed within the framework of PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium). The overall objective of PROTECT is to strengthen the monitoring of the benefit-risk of medicines in Europe. Work package 6 “validation on methods involving an extended audience” aims to test the transferability/feasibility of methods developed in other WPs (in particular WP2 and WP5) in a range of data sources owned or managed by Consortium Partners or members of the Extended Audience. The specific aims of this study within WP6 are: to evaluate the external validity of the study protocol on the risk of acute liver injury associated with the use of antibiotics by replicating the study protocol in another database, to study the impact of case validation on the effect estimate for the association between antibiotic exposure and acute liver injury. Of the selected drug-adverse event pairs selected in PROTECT, this study will concentrate on the association between antibiotic use and acute liver injury. On this topic, two sub-studies are performed: a descriptive/outcome validation study and an association study. The descriptive/outcome validation study has been conducted within the Utrecht Patient Oriented Database (UPOD).
    [Show full text]
  • Critically Important Antimicrobials for Human Medicine – 5Th Revision. Geneva
    WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) Critically Important Antimicrobials for Human Medicine 5th Revision 2016 Ranking of medically important antimicrobials for risk management of antimicrobial resistance due to non-human use Critically important antimicrobials for human medicine – 5th rev. ISBN 978-92-4-151222-0 © World Health Organization 2017, Updated in June 2017 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/ igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. Critically important antimicrobials for human medicine – 5th rev. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.
    [Show full text]
  • Pharmacological Drugs Inducing Ototoxicity, Vestibular Symptoms and Tinnitus: a Reasoned and Updated Guide
    European Review for Medical and Pharmacological Sciences 2011; 15: 601-636 Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide G. CIANFRONE1, D. PENTANGELO1, F. CIANFRONE2, F. MAZZEI1, R. TURCHETTA1, M.P. ORLANDO1, G. ALTISSIMI1 1Department of Otolaryngology, Audiology and Phoniatrics, “Umberto I” University Hospital, Sapienza University, Rome (Italy); 2Institute of Otorhinolaryngology, School of Medicine, Catholic University of the Sacred Heart, Rome (Italy) Abstract. – The present work on drug-in- Introduction duced ototoxicity, tinnitus and vertigo repre- sents the update and revision of a previous The panorama of the pharmacological origin guide to adverse drug reactions for italian physi- iatrogenic noxae able to induce either harmful cians (2005). The panorama of drug-induced side effects causing ototoxicity or symptoms ototoxic effects or just a symptomatology like tin- such as tinnitus or dizziness and vertigo has en- nitus or balance disturbances, without any harm- larged in recent years, thanks to a better knowl- ful consequence, has widened in the last few edge and a more specific attention of pharma- years. The reason for this is the progress of scien- ceutical firms and drug-control institutions. In tific knowledge, the increased awareness of the daily clinical practice, there is a need for the pharmaceutical companies and of the institutions, family physician and the ENT specialist or audi- ologist (also in consideration of the possible which supervise pharmaceutical production. medico-legal implications) to focus the attention Only through continuous updating and experi- on the possible risk of otological side effects. ence sharing it’s possible to offer patients the This would allow a clinical risk-benefit evalua- certainty of receiving the treatment that is appro- tion, weighing the possible clinical advantage in priate, safe and effective and based upon the their field of competence against possible oto- most credited clinical studies.
    [Show full text]
  • 6-Veterinary-Medicinal-Products-Criteria-Designation-Antimicrobials-Be-Reserved-Treatment
    31 October 2019 EMA/CVMP/158366/2019 Committee for Medicinal Products for Veterinary Use Advice on implementing measures under Article 37(4) of Regulation (EU) 2019/6 on veterinary medicinal products – Criteria for the designation of antimicrobials to be reserved for treatment of certain infections in humans Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. Introduction On 6 February 2019, the European Commission sent a request to the European Medicines Agency (EMA) for a report on the criteria for the designation of antimicrobials to be reserved for the treatment of certain infections in humans in order to preserve the efficacy of those antimicrobials. The Agency was requested to provide a report by 31 October 2019 containing recommendations to the Commission as to which criteria should be used to determine those antimicrobials to be reserved for treatment of certain infections in humans (this is also referred to as ‘criteria for designating antimicrobials for human use’, ‘restricting antimicrobials to human use’, or ‘reserved for human use only’). The Committee for Medicinal Products for Veterinary Use (CVMP) formed an expert group to prepare the scientific report. The group was composed of seven experts selected from the European network of experts, on the basis of recommendations from the national competent authorities, one expert nominated from European Food Safety Authority (EFSA), one expert nominated by European Centre for Disease Prevention and Control (ECDC), one expert with expertise on human infectious diseases, and two Agency staff members with expertise on development of antimicrobial resistance .
    [Show full text]