WO1996014849A1 - Utilisation des aminoglycosides pour le diagnostic des desordres formant barriere sang-air - Google Patents

Utilisation des aminoglycosides pour le diagnostic des desordres formant barriere sang-air Download PDF

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Publication number
WO1996014849A1
WO1996014849A1 PCT/DE1995/001578 DE9501578W WO9614849A1 WO 1996014849 A1 WO1996014849 A1 WO 1996014849A1 DE 9501578 W DE9501578 W DE 9501578W WO 9614849 A1 WO9614849 A1 WO 9614849A1
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WIPO (PCT)
Prior art keywords
aminoglycosides
tobramycin
blood
patients
disorders
Prior art date
Application number
PCT/DE1995/001578
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German (de)
English (en)
Inventor
Manfred Haider
Original Assignee
HAIDER, Angelika
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by HAIDER, Angelika filed Critical HAIDER, Angelika
Priority to AU38395/95A priority Critical patent/AU3839595A/en
Publication of WO1996014849A1 publication Critical patent/WO1996014849A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G01N33/9446—Antibacterials

Definitions

  • the invention relates to the use of aminoglycosides in aerosol form for the diagnosis of barrier disorders between the respiratory tract and blood vessels.
  • the permeability of the alveolocapillary membranes is greatly increased. If one could determine or assess the beginning and the course of this process at the bedside, this would greatly improve the treatment of patients, especially those with acute respiratory failure.
  • Radioisotopes have been used for this purpose.
  • the use and use of such radioisotopes is a burden among other things, the patients through the radioactive radiation.
  • such south punching systems require a high level of technical effort and are also only available to a limited extent.
  • the object of the present invention is to be able to detect acute lung diseases.
  • aminoglycosides do not pass normal cell walls, whereas in the presence of inflammation the permeability of the cell walls to these aminoglycosides is increased. It has now surprisingly been found that with the aid of such aminoglycosides it is possible to more or less exactly determine the permeability of alveolocapillary membranes and thus to detect and also to quantify a barrier disturbance between the alveoli and pulmonary vessels.
  • ammogivosides used according to the invention are known as known south punches which have hitherto been used exclusively for therapeutic purposes and in particular for the therapy of severe bacterial infections.
  • Amino glycosides of this type which can be used according to the invention are, for example, gentamycin, amikacin, netilmycin and tobramycin. the latter connection being preferred.
  • Tobramycin is a highly polar polycation with a molecular weight of 476 daltons. The binding of tobramycin to serum albums is negligible. Because of these properties, Tooramycm can be used as a maricer for aveolocapillary permeability. According to the invention, those ammoglycosides which have the properties described above can thus preferably be used. These ammogluccosides preferably have a molecular weight ⁇ approximately 1000 daltons. The use of these aminoglycosides according to the invention is now explained in more detail below with reference to the preferred compound tooramycin. This association stent somi ⁇ . representative of all use-aminoglycosides. According to the invention, tobramycin is administered to a patient via the
  • Tobracycin passes this barrier only to a small extent, so that the serum level of Tobramycin is low.
  • the serum concentration of tobramycin can be determined in a known manner with the help of commercially available tests, as will be explained in more detail below.
  • the Tobramyc values found in the blood it can be determined whether there is a barrier disorder or whether the permeability of the Aiveolocapillary membranes is increased or not.
  • the "in vitro" determined increase in the tobramycin concentration in the blood samples statements can be made as to whether the examined patient suffers from acute lung damage.
  • Such lung damage can be based on sepsis and on primary and acquired disorders of the immune system.
  • Such lung damage can also occur in patients who have undergone a surgical operation in which large areas of tissue have been injured, for example heart, lung and liver transplants.
  • tobramycin thus makes it possible to make statements about the type and extent of diseases of the lungs which are threatening to the liver, for example ARDS. These statements are of great medical importance.
  • tobramycin can provide valuable information, for example whether the formation of pulmonary edema is under control or not.
  • To administer tobramycin it is expediently inhaled in aerosol form.
  • Commercial tobramycin ampoules (Lilliy, Germany) can be diluted with distilled sterile water to a volume of 20 ml; a suitable dose is, for example, 6 to 10 mg / kg body weight.
  • Tobramycin is preferably administered in combination with a bronchodilator agent and / or a beta-2 agonist, which help improve the convection of the actual active substance into the peripheral lung sections.
  • a bronchodilator agent and / or a beta-2 agonist which help improve the convection of the actual active substance into the peripheral lung sections.
  • atropine derivatives as well
  • the formulation used should expediently be free of allergy-prone additives, for example sulfide stabilizers.
  • tobramycin is used for the diagnosis of barrier disorders of the type described.
  • Tooramycm a group of 7 patients
  • tobramycin ampoules (Lilliy, Germany) with sterile water up to a volume of 20 ml (8 mg / kg body weight) diluted.
  • the tobramycin was with
  • nebulized and inhaled by the patient were artificially ventilated.
  • the nebulizer was adjusted so that 20 ml of the heated aerosol with a mean particle size of 2.8 ⁇ m (0.5 to 65 ⁇ m) were dispensed within 20 minutes.
  • Blood samples (1.5 ml) were taken from the patients after the 10th and 20th minute after the start and thus during inhalation and every 10 minutes after the end of inhalation of the aerosol for a further period of 40 minutes.
  • the blood samples were centrifuged at 12,000 rpm for 10 min; the serum concentration of tobramycin was analyzed using a standard, commercially available test (TDx Abbott, Germany).
  • the tobramycin concentrations found after 10 and 20 min during inhalation of the aerosol are shown in Table 2.
  • Table 3 shows the values for the tobramycin concentration at the various times after the end of the inhalation.
  • the serum concentration increased.
  • Tobramycin in group A patients on the 10th or 20th min during aerosol inhalation 0.60 ⁇ 0.26 ⁇ g / ml or 1.1 ⁇ 0.28 ⁇ g / ml.
  • group B patients the tobramycin concentration was 0.11 ⁇ 0.05 ⁇ g / ml at the 10th minute and was unchanged at the 20th minute.
  • the serum tebramycin concentration gradually decreased to 0, ⁇ 6 ⁇ 0.25 ⁇ g / ml by the 60th minute in group A patients, while it increased slightly in group B patients.
  • the serum concentration of the tobramycin absorbed by inhalation accurately reflects the alveolocapillary permeability in patients with severe lung damage, in the present case ARDS. Since the tobramycin concentration increases only slightly in patients with less lung damage, the use of tobramycin according to the invention makes it possible to diagnose barrier disorders between the respiratory tract and blood vessels, even in the early, clinically not yet manifest stage. In other words, with the help of tobramycin it is possible to make statements about the size of the alveolocapillary permeability and thus about the presence and the course, etc. of severe lung damage.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Diabetes (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Conformément à l'invention, on utilise des aminoglycosides pour diagnostiquer des désordres formant barrière entre les voies respiratoires et les vaisseaux sanguins. A cet effet, ces aminoglycosides, en particulier la tobramycine, sont administrés par les voies respiratoires, sous forme d'aérosols. En cas de désordre formant barrière, les aminoglycosides passent plus ou moins sans entraves à travers les surfaces limites, entre les voies respiratoires et les vaisseaux sanguins. Un passage de quantités accrues d'aminoglycosides peut être mis en évidence par accroissement de leur concentration dans le sang, ce qui permet d'aboutir à des conclusions dans le cas d'affections pulmonaires aiguës.
PCT/DE1995/001578 1994-11-11 1995-11-09 Utilisation des aminoglycosides pour le diagnostic des desordres formant barriere sang-air WO1996014849A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU38395/95A AU3839595A (en) 1994-11-11 1995-11-09 Use of aminoglycosides to diagnose blood-air barrier disorders

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19944440391 DE4440391C1 (de) 1994-11-11 1994-11-11 Verwendung von Aminoglykosiden zur Diagnose von Schrankenstörungen
DEP4440391.7 1994-11-11

Publications (1)

Publication Number Publication Date
WO1996014849A1 true WO1996014849A1 (fr) 1996-05-23

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ID=6533112

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1995/001578 WO1996014849A1 (fr) 1994-11-11 1995-11-09 Utilisation des aminoglycosides pour le diagnostic des desordres formant barriere sang-air

Country Status (3)

Country Link
AU (1) AU3839595A (fr)
DE (1) DE4440391C1 (fr)
WO (1) WO1996014849A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU577781B2 (en) * 1983-04-28 1988-10-06 Mark Philip Best Lung imaging with radiolabelled agents
WO1989003672A1 (fr) * 1987-10-19 1989-05-05 Medipro Medicament comprenant l'association de polymyxine b, de netilmicine et d'amphotericine b administre par vaporisation
WO1989005139A1 (fr) * 1987-12-03 1989-06-15 Medipro Medicament comprenant l'association de colistine, de tobramycine et d'amphotericine b administree par vaporisation
WO1990006775A1 (fr) * 1988-12-14 1990-06-28 Liposome Technology, Inc. Nouvelle composition de liposomes non phospholipidique a liberation soutenue de medicaments

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU577781B2 (en) * 1983-04-28 1988-10-06 Mark Philip Best Lung imaging with radiolabelled agents
WO1989003672A1 (fr) * 1987-10-19 1989-05-05 Medipro Medicament comprenant l'association de polymyxine b, de netilmicine et d'amphotericine b administre par vaporisation
WO1989005139A1 (fr) * 1987-12-03 1989-06-15 Medipro Medicament comprenant l'association de colistine, de tobramycine et d'amphotericine b administree par vaporisation
WO1990006775A1 (fr) * 1988-12-14 1990-06-28 Liposome Technology, Inc. Nouvelle composition de liposomes non phospholipidique a liberation soutenue de medicaments

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE CHEMABS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; Y. VALCKE ET AL.: "The penetration of aminoglycosides into the alveolar lining fluid of rats: the effect of airway inflammation" *

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Publication number Publication date
AU3839595A (en) 1996-06-06
DE4440391C1 (de) 1996-05-09

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