DOCSLIB.ORG

CHARACTERIZATION of the INTESTINAL TRANSPORT PARAMETERS for SMALL Peptlde DRUGS*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
CHARACTERIZATION of the INTESTINAL TRANSPORT PARAMETERS for SMALL Peptlde DRUGS* Journal of Controlled Release, 13 (1990) 141-146 141 Elsevier Science Publishers B.V., Amsterdam CHARACTERIZATION OF THE INTESTINAL TRANSPORT PARAMETERS FOR SMALL PEPTlDE DRUGS* Doron I. Friedman and Gordon L. Amidon* College of Pharmacy, The University of Michigan, Ann Arbor, MI 48 109- 1065 (U.S. A .) (Received August 30, 1989; accepted in revised form January 5, 1990) Keywords: ACE inhibitors; j34actams; oral bioavailability of peptide drugs; carrier-mediated transport; absorption kinetics Several laboratories have recently shown that many peptides and peptide-similar drugs are well absorbed in the mammalian intestine via the peptide transport system for nutrient smallpeptide (dipeptides and tripeptides) absorption. This facilitated non-passive transport in the intestine is saturable and concentration dependent, and further characterized by the mutual inhibition of transport among the compounds. Peptide and peptide derivative drugs are often zwitterionic compounds, generally ionized at the intestinal pH and therefore are expected to undergo only limited passive absorption. Nonpassive and passive transport are independent and may occur simultaneously. Peptide drugs that have been shown to be transported by the peptide carrier systems are various &?actams, the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, lisinopril and SQ 29,852, TRH and its analogues, and alafosfaline and some of its analogues. The carrier characterization is based upon transport parameters, K, J,,, (or V,,.J and P, (Michaelis-Menten constant, maximal flux and the carrier permeability constant respec- tively) determined over the last years for several dipeptides, f3-lactam antibiotics and ACE inhibitors. INTRODUCTION and tripeptides. Larger peptides are hydrolyzed by the brush border enzymes before being ab- Proteins and peptides are hydrolyzed by pro- sorbed as tripeptides, dipeptides or amino acids. teolytic enzymes while traversing the G.I. sys- The peptide carrier is distinct from the amino tem to finally reach the intestinal absorptive acid transport carriers. The small peptide car- membrane either as readily absorbable amino rier transports dipeptides and tripeptides of acids or as short peptides [ 11. Uptake of the different amino composition and is versatile to- short peptides into the intestinal microvillus wards many structure modifications as will be cells is accomplished by the peptide carrier shown in this paper. Nevertheless, this peptide transport system and is restricted to dipeptides carrier has not yet been described in a way that enables structure-uptake relationship pre- *Paper presented at the Second International Symposium diction. on Disposition and Delivery of Peptide Drugs (F.I.P. Sat- Many peptide drugs which are derivatives of ellite Symposium) held at Leiden, The Netherlands, l-3 September 1989. dipeptides and tripeptides are absorbed in a fa- *To whom correspondence about this paper should be cilitated manner via the peptide carrier-me- addressed. diated transport system [2-121. Unlike large 0168-3659/90/$03.50 0 1990 - Elsevier Science Publishers B.V. 142 peptide and protein drugs, which are highly manner are thyrotrophin-releasing hormone susceptible to proteolytic enzymes and are cur- (TRH ) and its analogues which are tripeptide rently administered parenterally, small peptide and tripeptide derivatives [ 81 and alafosfalines or peptide-like drugs are more suitable for oral which comprise a unique group of antibiotics administration. Non=passive transport can undergoing hydrolysis concurrently with ab- provide an efficient route for absorption for sorption by the peptide carrier transport sys- these compounds which are generally charged tem [9]. More recently, several angiotensin or zwitterionic at the physiological pH and may converting enzyme (ACE) inhibitors which are not readily penetrate the lipophilic intestinal dipeptide and tripeptide derivatives were shown membrane. to be transported by the intestinal peptide car- Transport via the peptide carrier-mediated rier-mediated transport system and their system is a saturable and concentration depen- transport profile and Michaelis-Menten pa- dent phenomenon which is characterized by the rameters were defined [ 10-121. Michaelis-Menten constants K, and JmaX (or In this paper the carrier transport parame- V,,,). Uptake inhibition by other compounds ters L, Lax and J,,,/K, (P,) for the /3-lac- transported by the peptide carrier is typical of tam antibiotics and ACE inhibitors are re- this type of carrier-mediated transport. Al- viewed and compared in order to initiate a though apparent competitive inhibition seems structure-absorption characterization of the to occur, the inhibition mechanism for peptide intestinal small peptide carrier-mediated drugs has not yet been extensively studied. transport system. Passive transport of peptide derivative drugs may occur simultaneously with a non-passive transport and it is proportional to the relative hydrophobic character of the compound. While TRANSPORT PARAMETERS FOR SMALL passive transport may take place along the en- PEPTIDE DRUGS tire intestine, nonpassive transport via the pep- tide carrier may exhibit a site-specific absorp- tion profile due to the localization of the carrier Detailed transport parameters are available to the small intestine. for several hydrolysis stable dipeptides, P-lac- The in situ jejunal perfusion or ex uivo jejunal tam antibiotics and ACE inhibitors. The trans- rings and everted intestine have been fre- port parameters are the permeability parame- quently employed to characterize carrier-me- ters PCand P, for non-passive (carrier ) and for diated transport. Varying drug concentrations passive diffusion transport pathways, respec- are used to detect Michaelis-Menten uptake tively and the maximal transport rate V,,, (or behavior and to define the transport parame- J,,,) and the Michaelis-Menten constant, K,, ters, K, J,,, and P, (J,,,/K,). Transport in- for non-passive transport. The data presented hibitors are studied in order to validate non- in Table 1 are transport parameters derived passive transport and explore its mechanism. from in situ single-pass rat perfusion applying The penicillins which are D (Ala)-D (Ala) ana- the boundary layer solution for estimation of logues were the first peptide drugs identified to the aqueous permeability [ 131. be transported non-passively in the intestine by The interaction between the peptide and the the peptide carrier-mediated transport system. carrier is a primary factor in the nonpassive or Subsequently, the absorption mechanism of facilitated transport phenomenon. Unlike the other fi-lactams was recognized to involve a non- more specific amino acid carriers identified, the passive transport [ 2-71. Other groups of bioac- peptide carrier transports a variety of di- and tive compounds absorbed in a non-passive tripeptides composed of different amino acids 143 TABLE 1 Summary of permeability data for some dipeptides and peptide drugs p-lactams and ACE inhibitors (*-dimensionless pa- rameter, K,-Michaelis-Menten constant in mM, JL,, -maximal transport rate, Pr = J&,, /K,-the carrier transport param- eter, Pz-dimensionless passive parameter) Compound K, J&X p: pit Inhibitor Ref. Peptides Carnosine 12.9 6.62 0.51 3 Phe-Gly 1.29 6.87 5.33 3 P-Lactams Amoxicillin 0.058 0.044 0.558 0.76 21 Cefaclor 16.1 21.3 1.32 0.00 6 Cefadroxil 5.9 8.4 1.43 0.00 Cyclacillin, Gly-Gly 6 Cefatrizine 0.58 0.73 1.25 0.20 6 Cephalexin 7.2 9.1 1.30 0.00 Cyclacillin, Gly-Gly 6 Cephradine 1.48 1.57 1.06 0.30 Cephalexin, Gly-Leu 6 Cefixime 0.031 0.016 0.184 0.52 Carnosine, Gly-Pro 21 ACE inhibitors Captopril 5.9 12.3 2.08 1.00 Gly-Gly, Cephradine 10 Enalapril 0.07 0.13 1.9 0.35 Tyr-Gly, Cephradine 11 Lisinopril 0.082 0.032 0.39 0.00 Tyr-Gly, Cephradine 12 SQ 29,852 0.080 0.160 2.00 0.25 Tyr-Gly, Cephradine 12 and peptide-like drugs which bear various sub- MACROSCOPIC CORRELATION stitution groups and which are not necessarily natural peptides by their chemical structure. The transport parameters for several acid Although some evidence for the existence of stable p-lactam antibiotics are presented in Ta- multiple peptide carriers has been recently ble 1. The carrier permeability parameter, e or published [ 141, it has not been confirmed and S,,,/K,, is relatively constant for these D-lac- so remains to be resolved. The parameters pre- tam antibiotics while Jkax and Km vary more sented in Table 1 for peptide transport dem- significantly. The Km and S,,,, as summarized onstrate different “affinities” of the peptide for in Table 1, for the different P-lactams are cor- the carrier as well as variability with respect to related in Fig. 1 with the maximal plasma lev- stability against enzymatic hydrolysis. For ex- els, C,,,, in humans after a 500 mg oral dose. ample, carnosine (P-Ala-His) is very stable The C,,, values in Fig. 1 are the mean values of against enzymatic hydrolysis and therefore was the reported maximal plasma levels [ 151. A sig- extensively studied [ 31. nificant correlation between Km and C,,, after It is difficult to compare non-passive trans- oral administration of the different /3-lactams port parameters measured by different labora- is observed. The maximal plasma concentra- tories due to differing experimental approaches tion, C,,,, after a 500 mg oral dose for several and methods for the calculation of JmaX.Since j?-lactams increases as Km increases. Since P,, J,,, and J,,,/K, may be calculated for a spe- also increases proportionally, J*,/K, will not cific amount of dry or wet tissue weight, protein change significantly between the various P-lac- or intestinal length or surface area, a simple tams studied and the permeability constant of transformation and matching of the data is im- the carrier may therefore be assumed relatively possible. We will focus on results from our lab- constant. From this correlation it can be con- oratory for consistency [5,6,10-121. cluded that the maximal flux or the carrier ca- 144 15 For the ACE inhibitors, a linear relation is / shown in Fig.
Load more

Recommended publications
  • Pharmacokinetic Evaluation of Amoxicillin/Clavulanicacid And
    PHARMACOKINETIC EVALUATION OF AMOXICILLIN/CLAVULANICACID AND ANTACID INTERACTION Anab Fatima B.Pharm, M.Phil.(Pharmaceutics) Thesis submitted for the award of degree of Ph.D In Pharmaceutics DEPARTMENT OF PHARMACEUTICS FACULTY OF PHARMACY UNIVERSITY OF KARACHI. 1 2 In the name of ALLAH The most Beneficient and tha most Merciful………………. ALLAHUMA SALLEY ALA SYEDENA MAULANA MUHAMMEDUN WA ALA AALEHYY WA ASHABHI BARIK WASALLIM WA SALLO ALEHEY SURAT AL-FATIHAH 1. IN THE NAME OF ALLAH,THE MOST GRACIOUS,THE MOST MERCIFUL. 3 2. ALL THE PRAISES AND THANKS BE TO ALLAH,THE LORD OF THE A LAMIN(MANKIND,JINN AND ALL THAT EXIST). 3. THE MOST GRACIOUS,THE MOST MERCIFUL. 4. THE ONLY OWNER(AND THE ONLY RULING JUDGE)OF THE DAY OF RECOMPENSE(THE DAY OF RESURRECTION). 5. YOU(ALONE) WE WORSHIP,AND YOU(ALONE) WE ASK FOR HELP(FOR EACH AND EVERY THING). 6. GUIDE US TO STRAIGHT WAY. 7. THE WAY OF THOSE WHOM YOU HAVE BESTOWED YOUR GRACE,NOT(THE WAY) OF THOSE WHO EARNED YOUR ANGER NOR OF THOSE WHO WENT ASTRAY.(AAMEEN) 4 DEDICATED TO: My beloved Parentral Grand Father(late),Grand Mother(late),Parents and all those persons whose prayers bring me to this stage. ACKNOWLEDGEMENT “If ALLAH assist you, then there is none that can overcome you” (Holy Quran 3:160) All praise to Almighty Allah who gives me strength, confidence and courage to complete the thesis. I am heartiest thankful to my research supervisor Prof.Dr.S.Baqir.S.Naqvi for his valuable guidance, sincere advice, moral support and encouragement throughout the research project.
    [Show full text]
  • Consideration of Antibacterial Medicines As Part Of
    Consideration of antibacterial medicines as part of the revisions to 2019 WHO Model List of Essential Medicines for adults (EML) and Model List of Essential Medicines for children (EMLc) Section 6.2 Antibacterials including Access, Watch and Reserve Lists of antibiotics This summary has been prepared by the Health Technologies and Pharmaceuticals (HTP) programme at the WHO Regional Office for Europe. It is intended to communicate changes to the 2019 WHO Model List of Essential Medicines for adults (EML) and Model List of Essential Medicines for children (EMLc) to national counterparts involved in the evidence-based selection of medicines for inclusion in national essential medicines lists (NEMLs), lists of medicines for inclusion in reimbursement programs, and medicine formularies for use in primary, secondary and tertiary care. This document does not replace the full report of the WHO Expert Committee on Selection and Use of Essential Medicines (see The selection and use of essential medicines: report of the WHO Expert Committee on Selection and Use of Essential Medicines, 2019 (including the 21st WHO Model List of Essential Medicines and the 7th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization; 2019 (WHO Technical Report Series, No. 1021). Licence: CC BY-NC-SA 3.0 IGO: https://apps.who.int/iris/bitstream/handle/10665/330668/9789241210300-eng.pdf?ua=1) and Corrigenda (March 2020) – TRS1021 (https://www.who.int/medicines/publications/essentialmedicines/TRS1021_corrigenda_March2020. pdf?ua=1). Executive summary of the report: https://apps.who.int/iris/bitstream/handle/10665/325773/WHO- MVP-EMP-IAU-2019.05-eng.pdf?ua=1.
    [Show full text]
  • Computational Antibiotics Book
    Andrew V DeLong, Jared C Harris, Brittany S Larcart, Chandler B Massey, Chelsie D Northcutt, Somuayiro N Nwokike, Oscar A Otieno, Harsh M Patel, Mehulkumar P Patel, Pratik Pravin Patel, Eugene I Rowell, Brandon M Rush, Marc-Edwin G Saint-Louis, Amy M Vardeman, Felicia N Woods, Giso Abadi, Thomas J. Manning Computational Antibiotics Valdosta State University is located in South Georgia. Computational Antibiotics Index • Computational Details and Website Access (p. 8) • Acknowledgements (p. 9) • Dedications (p. 11) • Antibiotic Historical Introduction (p. 13) Introduction to Antibiotic groups • Penicillin’s (p. 21) • Carbapenems (p. 22) • Oxazolidines (p. 23) • Rifamycin (p. 24) • Lincosamides (p. 25) • Quinolones (p. 26) • Polypeptides antibiotics (p. 27) • Glycopeptide Antibiotics (p. 28) • Sulfonamides (p. 29) • Lipoglycopeptides (p. 30) • First Generation Cephalosporins (p. 31) • Cephalosporin Third Generation (p. 32) • Fourth-Generation Cephalosporins (p. 33) • Fifth Generation Cephalosporin’s (p. 34) • Tetracycline antibiotics (p. 35) Computational Antibiotics Antibiotics Covered (in alphabetical order) Amikacin (p. 36) Cefempidone (p. 98) Ceftizoxime (p. 159) Amoxicillin (p. 38) Cefepime (p. 100) Ceftobiprole (p. 161) Ampicillin (p. 40) Cefetamet (p. 102) Ceftoxide (p. 163) Arsphenamine (p. 42) Cefetrizole (p. 104) Ceftriaxone (p. 165) Azithromycin (p.44) Cefivitril (p. 106) Cefuracetime (p. 167) Aziocillin (p. 46) Cefixime (p. 108) Cefuroxime (p. 169) Aztreonam (p.48) Cefmatilen ( p. 110) Cefuzonam (p. 171) Bacampicillin (p. 50) Cefmetazole (p. 112) Cefalexin (p. 173) Bacitracin (p. 52) Cefodizime (p. 114) Chloramphenicol (p.175) Balofloxacin (p. 54) Cefonicid (p. 116) Cilastatin (p. 177) Carbenicillin (p. 56) Cefoperazone (p. 118) Ciprofloxacin (p. 179) Cefacetrile (p. 58) Cefoselis (p. 120) Clarithromycin (p. 181) Cefaclor (p.
    [Show full text]
  • Cephalosporin Administration to Patients with a History of Penicillin Allergy Adverse Reactions to Drugs, Biologicals and Latex Committee
    Work group report May, 2009 Cephalosporin Administration to Patients with a History of Penicillin Allergy Adverse Reactions to Drugs, Biologicals and Latex Committee Work Group Members : Roland Solensky, MD FAAAAI, Chair Aleena Banerji, MD Gordon R. Bloomberg, MD FAAAAI Marianna C. Castells, MD PhD FAAAAI Paul J. Dowling, MD George R. Green, MD FAAAAI Eric M. Macy, MD FAAAAI Myngoc T. Nguyen, MD FAAAAI Antonino G. Romano, MD PhD Fanny Silviu-Dan, MD FAAAAI Clifford M. Tepper, MD FAAAAI INTRODUCTION Penicillins and cephalosporins share a common beta-lactam ring structure, and hence the potential for IgE-mediated allergic cross-reactivity. Allergic cross-reactivity between penicillins and cephalosporins potentially may also occur due to presence of identical or similar R-group side chains, in which case IgE is directed against the side chain, rather the core beta-lactam structure. This work group report will address the administration of cephalosporins in patients with a history of penicillin allergy. First, published data will be reviewed regarding 1) cephalosporin challenges of patients with a history of penicillin allergy (without preceding skin testing or in vitro testing), and 2) cephalosporin challenges of patients proven to have a type I allergy to penicillins (via positive penicillin skin test, in vitro test or challenge). Secondly, 1 2/9/2011 recommendations on cephalosporin administration to patients with a history of penicillin allergy will be presented. Unless specifically noted, the term ‘penicillin allergy’ will be used to indicate an allergy to one or more of the penicillin-class antibiotics, not just to penicillin itself. The following discussion includes references, in certain clinical situations, to performing cephalosporin graded challenges in patients with a history of penicillin allergy.
    [Show full text]
  • European Surveillance of Healthcare-Associated Infections in Intensive Care Units
    TECHNICAL DOCUMENT European surveillance of healthcare-associated infections in intensive care units HAI-Net ICU protocol Protocol version 1.02 www.ecdc.europa.eu ECDC TECHNICAL DOCUMENT European surveillance of healthcare- associated infections in intensive care units HAI-Net ICU protocol, version 1.02 This technical document of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Carl Suetens. In accordance with the Staff Regulations for Officials and Conditions of Employment of Other Servants of the European Union and the ECDC Independence Policy, ECDC staff members shall not, in the performance of their duties, deal with a matter in which, directly or indirectly, they have any personal interest such as to impair their independence. This is version 1.02 of the HAI-Net ICU protocol. Differences between versions 1.01 (December 2010) and 1.02 are purely editorial. Suggested citation: European Centre for Disease Prevention and Control. European surveillance of healthcare- associated infections in intensive care units – HAI-Net ICU protocol, version 1.02. Stockholm: ECDC; 2015. Stockholm, March 2015 ISBN 978-92-9193-627-4 doi 10.2900/371526 Catalogue number TQ-04-15-186-EN-N © European Centre for Disease Prevention and Control, 2015 Reproduction is authorised, provided the source is acknowledged. TECHNICAL DOCUMENT HAI-Net ICU protocol, version 1.02 Table of contents Abbreviations ...............................................................................................................................................
    [Show full text]
  • Directed Molecular Evolution of Fourth-Generation Cephalosporin Resistance in Wellington Moore Iowa State University
    Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2011 Directed molecular evolution of fourth-generation cephalosporin resistance in Wellington Moore Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Medical Sciences Commons Recommended Citation Moore, Wellington, "Directed molecular evolution of fourth-generation cephalosporin resistance in" (2011). Graduate Theses and Dissertations. 10107. https://lib.dr.iastate.edu/etd/10107 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Directed molecular evolution of fourth-generation cephalosporin resistance in Salmonella and Yersinia by Wellington Moore A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Biomedical Science (Pharmacology) Program of Study Committee: Steve Carlson, Major Professor Timothy Day Ronald Griffith Iowa State University Ames, Iowa 2011 ii TABLE OF CONTENTS LIST OF FIGURES………………………………………………………………………iii LIST OF TABLES………………………………………………………………………..iv ABSTRACT……………………………………………………………………………….v CHAPTER 1. INTRODUCTION…………………………………………………………1 Review of B-Lactam antimicrobials………………………………...………1
    [Show full text]
  • United States Patent 19 11 Patent Number: 5,763,603 Trickes 45 Date of Patent: Jun
    USOO5763603A United States Patent 19 11 Patent Number: 5,763,603 Trickes 45 Date of Patent: Jun. 9, 1998 54 CRYSTALLINE TAZOBACTAM, AND ITS 4,912,211 3/1990 Bonfanti................................. 540/222 PRODUCTION AND USE FOREIGN PATENT DOCUMENTS (75) Inventor: Georg Trickes, Loerrach, Germany 63-66187 3/1988 Japan. 73) Assignee: Taiho Pharmaceutical Co., Ltd., OTHER PUBLICATIONS Tokyo, Japan Chemical Patents Index Basic Abstracts Journal, Section (21) Appl. No.: 403829 B:FARMDOC, 1988, Derwent Publications, week 88.18, 29 22 PCT Filed: Nov. 2, 1994 Jun. 1988, 88-122648/18. 86 PCT No.: PCTAJP94/01855 Primary Examiner-Mukund J. Sham Assistant Examiner-Pavanaram K. Sripada S371 Date: Mar 21, 1995 Attorney, Agent, or Firm-Sughrue. Mion. Zinn. Macpeak S 102(e) Date: Mar. 21, 1995 & Seas, PLLC 87 PCT Pub. No.: WO95/12601 57 ABSTRACT Crystalline sodium 20-methyl-2B-(1,2,3-triazol-1-yl) PCT Pub. Date: May 11, 1995 -methylpenan-3o-carboxylate-1,1-dioxide monohydrate 30 Foreign Application Priority Data (crystalline tazobactam sodium monohydrate) obtainable by adding to a concentrated aqueous solution of sodium Nov. 6, 1993 EP European Pat. Off. .............. 93.18.016 20-methyl-23-(1,2,3-triazol-1-yl)-methylpenam-30 (51) Int. Cl. ... ... CO7D 499/00; A61K 31/425 carboxylate-1,1-dioxide (tazobactam sodium) a solvent 52) U.S. Cl. ............................................ 540/310: 514/210 selected from acetone and ethanol in an amount correspond 58) Field of Search .............................. 540/310; 514/210 ing to a solvent to water ratio of between about 95:5 and 99:1 v/v and crystallizing the desired product from the solvent 56) References Cited mixture.
    [Show full text]
  • The New Fifth-Generation Cephalosporins – a Balance Between Safety and Efficacy
    REVIEWS Ref: Ro J Pharm Pract. 2020;13(3) DOI: 10.37897/RJPhP.2020.3.2 The new fifth-generation cephalosporins – a balance between safety and efficacy Aura Rusu1, Ioana-Andreea Lungu2 1 Pharmaceutical and Therapeutical Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania 2 Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania Abstract Cephalosporins are beta-lactam antibiotics classified into five generations. The newest generation has three representa- tives: ceftaroline fosamile, the combination ceftolozane/tazobactam (cephalosporin/beta-lactamase inhibitor), and ceftobi- prole medocaril. These new cephalosporins are valuable anti-infective agents, with potent activity against multidrug-re- sistant bacteria, and with a positive balance between benefits and side effects. However, the fifth-generation cephalosporins should be judiciously used to prevent the occurrence of bacterial resistance phenomenon. Keywords: cephalosporins, ceftaroline, ceftolozane, ceftobiprole, MRSA, community-acquired pneumonia, complicated skin and soft tissue infections INTRODUCTION emerged as a result of increased only, in the situation where other Cephalosporins (CFs) are beta- bacterial resistance to classical antibacterial drugs were not lactam antibiotics with numerous antibiotics. Based on the efficient. representatives widely used in the antimicrobial activity, the CFs are therapy
    [Show full text]
  • Antimicrobial Composition
    Europa,schesP_ MM M II M MM 1 1 M Ml MM M Ml J European Patent Office .ha no © Publication number: 0 384 41 OBI Office europeen, desJ brevets © EUROPEAN PATENT SPECIFICATION © Date of publication of patent specification: 17.05.95 © Int. CI.6: A61 K 31/545, A61 K 31/43, //(A61K31/545,31:43) © Application number: 90103266.4 @ Date of filing: 20.02.90 The file contains technical information submitted after the application was filed and not included in this specification © Antimicrobial composition. ® Priority: 21.02.89 JP 41286/89 9-1, Kamimutsuna 3-chome 14.04.89 JP 94460/89 Okazaki-shi, Aichi (JP) @ Date of publication of application: Inventor: Sanada, Mlnoru, c/o BANYU PHARM. 29.08.90 Bulletin 90/35 CO., LTD. OKAZAKI RES. LABORATORY, © Publication of the grant of the patent: 9-1, Kamimutsuna 3-chome 17.05.95 Bulletin 95/20 Okazaki-shi, Aichi (JP) © Designated Contracting States: Inventor: Nakagawa, Susumu, c/o BANYU CH DE FR GB IT LI NL PHARM. CO., LTD. OKAZAKI RES. LABORATORY, © References cited: 9-1, Kamimutsuna 3-chome EP-A- 0 248 361 Okazaki-shi, Aichi (JP) UNLISTED DRUGS, vol. 37, no. 2, February Inventor: Tanaka, Nobuo, c/o BANYU PHARM. 1985, Chatham, New Jersey, US; "Zienam CO., LTD. 250". 2-3, Nihonbashi Honcho 2-chome Chuo-ku, © Proprietor: BANYU PHARMACEUTICAL CO., Tokyo (JP) LTD. Inventor: Inoue, Matsuhisa 2-3, Nihonbashi Honcho 2-chome 3076-3, Oaza-Tokisawa 00 Chuo-ku, Tokyo (JP) Fujlmi-mura, Seta-gun, @ Inventor: Matsuda, Kouji, c/o BANYU PHARM. Gunma (JP) CO., LTD.
    [Show full text]
  • Separation and Purification of Pharmaceuticals and Antibiotics [Table IX-1-1] Principal Antibiotics Penicillin-G (Benzylpenicillin), Oxacillin, Chlox- 1
    Separation and Purification of Pharmaceuticals and Antibiotics [Table IX-1-1] Principal Antibiotics Penicillin-G (benzylpenicillin), Oxacillin, Chlox- 1. Antibiotics acillin, Dichloxacillin, Nafcillin, Methicillin, (1) Outline Amoxicillin, Ampicillin, Ticarcillin, Piperacillin, Penicillins aspoxicillin, Antibiotics are "chemical substances produced by microorganisms Ciclacillin, Sulbenicillin, Talampicillin, which, in minute quantities, inhibit or suppress the proliferation of other Bacampicillin, Pivmecillinam, lenampicillin, microorganisms". This is defined in 1942 by Selman Abraham Waksman β-Lactams Phenethicillin, Carbenicillin etc, in the USA. Antibiotics were developed in Britain following the discovery Cephalosporin C of Penicillin in 1929 by Alexander Fleming: He found that Blue mold, Cefazolin, Cefatrizine, Cefadroxil, Cefalexin, Cephalosporins Cefaloglycin, Cefalothin, Cefaloridine, Cefoxitin, Penicillium, dissolves Staphylococcus staphylococci and inhibits its Cefotaxime, Cefoperazone, Ceftizoxime, Cefmet- growth and he named the extract from Penicillium as Penicillin. Many azole, Cefradine, Cefroxadine etc. new antibiotics have been found since 1940’s, and there are more than Other β-lactams 1,500 antibiotics. Principal ones are listed in Table IX-1-1. Kanamycins Amikacin, Kanamycin, Dibekacin Most of these antibiotics are manufactured by fermentation or by Gentamycins, Gentamicin, Micronomicin semi-synthesis that combines fermentation and organic synthesis, though Sisomycins chloramphenicol is by synthesis. Fermentation is carried out by Acti- Streptomycins Streptomycin Aminoglycosides nomycetes, mold (hyphomycetes) or bacteria in culture media with glu- Spectinomycins Spectinomycin cose, sucrose, lactose, starch or dextrin as carbon source, with nitrate, Fradiomycins Fradiomycin, ammonium salt, corn steep liquor, peptone, meat extract or yeast extract Astromicins Astromicin as nitrogen source and with a little amount of inorganic salts. Erythromycin, Oleandomycin, Carbomycin, Penicillin-type antibiotics are manufactured by semi-synthesis, i.e.
    [Show full text]
  • Analysis of Amoxicillin and Clavulanic Acid by UPLC-MS/MS in Human Plasma for Pharmacokinetic Application
    JOURNAL OF MODERN DRUG DISCOVERY AND DRUG DELIVERY RESEARCH Journal homepage: http://scienceq.org/Journals/JMDDR.php Research Article Open Access Analysis of Amoxicillin and Clavulanic Acid by UPLC-MS/MS in Human Plasma for Pharmacokinetic Application Darshan V. Chaudhary1, Daxesh P. Patel1, Jaivik V. Shah1, Priyanka A. Shah1, Vijay R. Patel2, Pranav S. Shrivastav1* 1. Department of Chemistry, School of Sciences, Gujarat University, Navrangpura, Ahmedabad- 380009, India . 2. Shri R. K Parikh Arts & Science College, Petlad-388450, Gujarat, India. *Corresponding author: Pranav S. Shrivastav, Tel.: +91-9925471963, E-mail: [email protected] Received: January 2, 2015, Accepted: February 5, 2015 Published: February 6, 2015. ABSTRACT A bioanalytical method for the simultaneous quantification of amoxicillin (AMX) and clavulanic acid (CLV) in human plasma using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been successfully developed and validated. The analytes and amoxicillin-d4 as internal standard were extracted from 100 µL plasma by solid phase extraction using Phenomenex Strata-X cartridges. Chromatographic separation was done on UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm) column using acetonitrile: 2.0 mM ammonium formate in water (85:15, v/v) as the mobile phase at a flow rate of 0.400 mL/min under isocratic condition. Mass spectrometric detection was by multiple reaction monitoring with an electrospray ionization source in the negative ionization mode. The response of the method was linear in the analytical range of 10.0-10000 (r2 ≥ 0.9997) and 2.5-2500 ng/mL (r2 ≥ 0.9993) for AMX and CLV respectively. Intra- and inter batch accuracy and precision (% CV) were in the range of 96.1-103.2 % and 1.48-5.88 respectively for both the analytes.
    [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]