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DOI: 10.1055/s-2008-1038128
Perspektiven in der Inhalationstherapie[1]
Perspectives in the Inhalative Administration of DrugsPublication History
eingereicht 4.1.2008
akzeptiert 30.1.2008
Publication Date:
06 June 2008 (online)

Zusammenfassung
Die inhalative Applikation von Medikamenten wird neue Anwendungsgebiete sowohl bei Lungenerkrankungen als auch in der systemischen Therapie gewinnen. Die Inhalation von Antibiotika ist bereits Standard in der Therapie der zystischen Fibrose. Bei Bronchiektasen, der schweren COPD mit bakterieller Kolonisation und bei invasiv beatmeten Patienten gibt es Hinweise auf die Wirksamkeit der Inhalation von Aminoglykosiden. Die Inhalation zur Substitution von alpha 1-Antitrypsin ist der i. v. Gabe beim Lungenemphysem bezüglich der intrapulmonalen Dosis überlegen. Auch wenn das inhalative Insulin wieder vom deutschen Markt genommen wurde, besteht weiter eine intensive Forschungstätigkeit auf dem Gebiet der Inhalation von Insulin und Heparin zur systemischen Therapie des Diabetes mellitus bzw. der Antikoagulation.
Abstract
Administration of drugs via the inhalation route will find new indications in the therapy for lung diseases. Furthermore, aerosolised drugs are of increasing interest for systemic treatment. The inhalation of antibiotics is already a well established therapy in cystic fibrosis. In bronchiectasis, severe COPD with bacterial airway colonisation and in mechanically ventilated patients, aerosolised aminoglycosides may provide benefit. Substitution of alpha1-antitrypsin in lung emphysema via inhalation seems to be superior to the intravenous administration. Inhaled insulin has currently been withdrawn from the market in spite of being approved by FDA and EMEA. However, intensive scientific research is still ongoing and many clinical studies are underway in the field of the inhalation of insulin, heparins and other systemic treatments.
Literatur
- 1
Buhl R, Berdel D, Criee C P. et al .
Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma bronchiale.
Pneumologie.
2006;
60
139-177
Reference Ris Wihthout Link
- 2
Vogelmeier C, Buhl R, Criee C P. et al .
Leitlinie der Deutschen Atemwegsliga und der Deutschen Gesellschaft zur Diagnostik
und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem.
Pneumologie.
2007;
61
323-340
Reference Ris Wihthout Link
- 3
Ratjen F, Doering G, Nikolaizik W H.
Effect of inhaled tobramycin on early pseudomonas aeruginosa colonisation in patients
with cystic fibrosis.
Lancet.
2001;
358
983-984
Reference Ris Wihthout Link
- 4
Ramsey B W, Pepe M S, Quan J M. et al .
Intermittent administration of inhaled tobramycin in patients with cystic fibrosis.
N Engl J Med.
1999;
340
23-30
Reference Ris Wihthout Link
- 5
Ratjen F, Rietschel E, Kasel D. et al .
Pharmakokinetics of inhaled colistin in patients with cystic fibrosis.
J Antimicrob Chemother.
2006;
57
306-311
Reference Ris Wihthout Link
- 6
Mendelman P M, Smith A L, Kenny A M. et al .
Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis or bronchiectasis:
comparison with activity in serum.
Am Rev Respir Dis.
1985;
132
761-765
Reference Ris Wihthout Link
- 7
Burns J L, Van-Dalfsen J M, Shawar R M. et al .
Effect of chronic intermittent administration of inhaled tobramycin on respiratory
microbial flora in patients with cystic fibrosis.
J Infect Dis.
1999;
179
1190-1196
Reference Ris Wihthout Link
- 8
Barclay M L, Begg E J, Chambers S T. et al .
Adaptive resistance to tobramycin in pseudomonas aeruginosa lung infection in cystic
fibrosis.
J Antimicrobial Chemotherapy.
1996;
37
1155-1164
Reference Ris Wihthout Link
- 9
Doering G, Conway S P, Heijerman H GM. et al .
Antibiotic therapy against pseudomonas aeruginosa in cystic fibrosis: a European consensus.
Eur Respir J.
2000;
16
749-767
Reference Ris Wihthout Link
- 10
Smith A L, Fiel S B, Mayer-Hamblett N. et al .
Susceptibility testing of pseudomonas aeruginosa isolates and clinical response to
parenteral antibiotic administration: lack of association in cystic fibrosis.
Chest.
2003;
123
1495-1502
Reference Ris Wihthout Link
- 11
Westerman E M, De Boer A H, Le Brun P P. et al .
Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot
study.
J Cyst Fibros.
2007;
6
284-292
Reference Ris Wihthout Link
- 12
Geller D E, Konstan M W, Smith J. et al .
Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and
safety.
Pediatr Pulmonol.
2007;
42
307-313
Reference Ris Wihthout Link
- 13
Gibson R L, Retsch-Bogart G Z, Oermann C. et al .
Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in
patients with cystic fibrosis.
Pediatr Pulmonol.
2006;
41
656-665
Reference Ris Wihthout Link
- 14
Barker A F.
Bronchiectasis.
N Engl J Med.
2002;
346
1383-1393
Reference Ris Wihthout Link
- 15
Murphy T F, Sethi S.
Bacterial infection in chronic obstructive pulmonary disease.
Am Rev Respir Dis.
1992;
146
1067-1083
Reference Ris Wihthout Link
- 16
Kohlhäufl M, Scheuch G, Häußinger K.
Antimikrobielle Aerosoltherapie bei Bronchiektasen?.
Pneumologie.
2004;
58
499-504
Reference Ris Wihthout Link
- 17
Scheinberg P, Shore E.
A pilot study of the safety and efficacy of tobramycin solution for inhalation in
patients with severe bronchiectasis.
Chest.
2005;
127
1420-1426
Reference Ris Wihthout Link
- 18
Drobnic M E, Sune P, Montoro J B. et al .
Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic
bronchial infection with pseudomonas aeruginosa.
Ann Pharmacother.
2005;
39
39-44
Reference Ris Wihthout Link
- 19
Bilton D, Henig N, Morrissey B.
Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of pseudomonas
aeruginosa infection in adult bronchiectasis.
Chest.
2006;
130
1503-1510
Reference Ris Wihthout Link
- 20
Soler-Cataluna J J, Martinez-Garcia M A, Roman S anchez . et al .
Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary
disease.
Thorax.
2005;
60
925-931
Reference Ris Wihthout Link
- 21
Calverley P, Anderson J A, Celli B. et al .
Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary
disease.
N Engl J Med.
2007;
356
775-789
Reference Ris Wihthout Link
- 22
Patel I S, Seemungal T AR, Wilks M. et al .
Relationship between bacterial colonisation and the frequency, character, and severity
of COPD exacerbations.
Thorax.
2002;
57
759-764
Reference Ris Wihthout Link
- 23
Wilkinson T M, Patel I S, Wilks M. et al .
Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2003;
167
090-1095
Reference Ris Wihthout Link
- 24
Calverley P M, Spencer S, Willits L. et al .
Withdrawal from treatment as an outcome in the ISOLDE study of COPD.
Chest.
2003;
124
1350-1356
Reference Ris Wihthout Link
- 25
Aaron S D, Vandemheen K L, Fergusson D. et al .
Tiotropium in Combination with Placebo, Salmeterol, or Fluticasone-Salmeterol for
Treatment of Chronic Obstructive Pulmonary Disease.
Ann Intern Med.
2007;
146
545-555
Reference Ris Wihthout Link
- 26
Szafranski W, Cukier A, Ramirez A. et al .
Efficacy and safety of budesonide/formoterol in the management of chronic obstructive
pulmonary disease.
Eur Respir J.
2003;
21
74-81
Reference Ris Wihthout Link
- 27
Patel I S, Vlahos I, Wilkinson T M. et al .
Bronchiectasis, Exacerbation Indices, and Inflammation in Chronic Obstructive Pulmonary
Disease.
Am J Respir Crit Care Med.
2004;
170
400-407
Reference Ris Wihthout Link
- 28
Tsang K W, Chan K, Ho P. et al .
Sputum elastase in steady-state bronchiectasis.
Chest.
2000;
117
420-426
Reference Ris Wihthout Link
- 29
Stockley R A, Bayley D, Hill S L. et al .
Assessment of airway neutrophils by sputum colour: correlation with airways inflammation.
Thorax.
2001;
56
366-372
Reference Ris Wihthout Link
- 30
Sethi S.
Infection etiology of acute exacerbations of chronic bronchitis.
Chest.
2000;
117 (Suppl. 2)
380S-385S
Reference Ris Wihthout Link
- 31
Rohde G, Wiethege A, Borg I. et al .
Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring
hospitalisation - a case control study.
Thorax.
2003;
58
37-42
Reference Ris Wihthout Link
- 32
Rohde G, Schlosser B, Arinir U. et al .
Die Rolle von Atemwegsinfektionen bei der chronisch-obstruktiven Lungenerkrankung.
Med Klinik.
2007;
102
893-898
Reference Ris Wihthout Link
- 33
Langer M, Mosconi P, Cigada M. et al .
Long-term respiratory support and risk of pneumonia in critically ill patients. Intensive
care unit group of infection control.
Am Rev Respir Dis.
1989;
140
302-305
Reference Ris Wihthout Link
- 34
MacIntyre N R, Rubin B.
Should aerosolized antibiotics be administered to prevent or treat ventilator-associated
pneumonia in patients who do not have cystic fibrosis?.
Respiratory care.
2007;
52
416-421
Reference Ris Wihthout Link
- 35
Palmer L B, Smaldone G C, Simon S R. et al .
Aerosolized antibiotics in mechanically ventilated patients: delivery and response.
Crit Care Med.
1998;
26
31-39
Reference Ris Wihthout Link
- 36
Liberati A, D’Amico R, Pifferi S. et al .
Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults
receiving intensive care.
Cochrane Database Syst Rev.
2004;
1
CD000022
Reference Ris Wihthout Link
- 37
Nieuwenhoven C A Van, Buskens E, Bergmans D C. et al .
Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia
in intensive care units.
Crit Care Med.
2004;
32
126-130
Reference Ris Wihthout Link
- 38
Badia J R, Soy D, Adrover M. et al .
Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive
care unit (ICU) patients.
Journal of Antimicrobial Chemotherapy.
2004;
54
508-514
Reference Ris Wihthout Link
- 39
Crystal R G, Brantly M L, Hubbard R C.
The alpha1- antitrysin Gene and its mutations.
Chest.
1989;
95
196
Reference Ris Wihthout Link
- 40
Perlmutter D H, Pierce J A.
The alpha1-antitrypsin gene and emphysema.
J Appl Physiol.
1989;
257
L 147
Reference Ris Wihthout Link
- 41
Pierce J A.
Antitrypsin and emphysema.
JAMA.
1988;
259
2890
Reference Ris Wihthout Link
- 42
Wewers M D, Casolaro M A, Sellers S E. et al .
Replacement therapy for alpha1-antitrypsin deficiency associated with emphysema.
N Engl J Med.
1987;
316
1055-1062
Reference Ris Wihthout Link
- 43
Hubbard R C, Crystal R G.
Augmentation therapy of alpha 1-antitrypsin deficiency.
Eur Respir J.
1990;
9
44s-52s
Reference Ris Wihthout Link
- 44
Wencker M, Banik N, Buhl R. et al .
Langzeittherapie des alpha1-Antitrypsin-mangelassoziierten Lungenemphysems mit humanen
alpha1-Antitrypsin.
Pneumologie.
1998;
52
545-552
Reference Ris Wihthout Link
- 45
Kropp J, Wencker M, Hotze A. et al .
Inhalation of [123I]alpha1-protease inhibitor: toward a new therapeutic concept of
alpha1-protease inhibitor deficiency?.
J Nucl Med.
2001;
42
744-751
Reference Ris Wihthout Link
- 46
Hubbard R C, Crystal R G.
Strategies for aerosol therapy of alpha1-antitrypsin deficiency by the aerosol route.
Lung.
1990;
Suppl
565-578
Reference Ris Wihthout Link
- 47
Cantin A M, Woods D E.
Aerosolized prolastin supresses bacterial proliferation in a model of chronic Pseudomonas
aeruginosa lung infection.
Am J Respir Crit Care Med.
1999;
160
1130-1135
Reference Ris Wihthout Link
- 48
Vogelmeier C, Kirlath I, Warrington S. et al .
The intrapulmonary half-life and safety of aerosolized a1-protease inhibitor in normal
volunteers.
Am J Respir Crit Care Med.
1997;
155
536-541
Reference Ris Wihthout Link
- 49
Hubbard R C, McElvaney N G, Sellers S E. et al .
DNA-produced alpha 1-antitrypsin administered by aerosol augments lower respiratory
tract antineutrophil elastase defenses in individuals with alpha 1-antitrypsin deficiency.
J Clin Invest.
1989;
84
1349-1354
Reference Ris Wihthout Link
- 50
Hubbard R C, Brantly M L, Sellers S E. et al .
Anti-neutrophil-elastase defenses of the lower respiratory tract in alpha 1-antitrypsin
deficiency directly augmented with an aerosol of alpha 1-antitrypsin.
Ann Intern Med.
1989;
111
206-212
Reference Ris Wihthout Link
- 51
Itoh H, Ishii Y, Maeda H. et al .
Clinical observations of aerosol deposition in patients with airway obstruction.
Chest.
1981;
80
837-840
Reference Ris Wihthout Link
- 52
Sweeney T D, Brain J D, Leavitt S A. et al .
Emphysema alters the deposition pattern of inhaled particles in hamsters.
Am J Pathol.
1987;
128
19
Reference Ris Wihthout Link
- 53 Schulz H, Brand P, Heyder J. Particle deposition in the respiratory tract. In: Gehr P, Heyder J, editor. Particle-lung interactions. New York, Basel: Dekker 2000: 229-290
Reference Ris Wihthout Link
- 54
Brand P, Friemel I, Meyer T. et al .
Total deposition of therapeutic particles during spontaneous and controlled inhalations.
J Pharmaceut Sci.
2000;
89
724-731
Reference Ris Wihthout Link
- 55
Brand P, Maas Enriquez M, Meyer T. et al .
Neue Strategien zur kontrollierten Inhalation von alpha 1-Antitrypsin.
Pneumologie.
2003;
57
153-158
Reference Ris Wihthout Link
- 56
Brand P, Häußinger K, Meyer T. et al .
Intrapulmonary distribution of deposited particles.
J Aerosol Med.
1999;
12
275-284
Reference Ris Wihthout Link
- 57
Brand P, Meyer T, Sommerer K. et al .
Alveolar deposition of monodisperse aerosol particles in the lung of patients with
COPD.
Exp Lung Res.
2002;
28 (1)
39-54
Reference Ris Wihthout Link
- 58
Sommerer K, Meyer T, Brand P. et al .
Evaluation of an optimal device for peripheral deposition in patients with lung emphysema.
Drug delivery to the lungs.
2001;
12
171-174
Reference Ris Wihthout Link
- 59
Müllinger B, Meyer T, Sommerer K. et al .
Patient individualized inhalation optimizes peripheral lung deposition.
Drug delivery to the lungs.
2001;
12
23-26
Reference Ris Wihthout Link
- 60
Griese M, Ramakers J, Krasselt A. et al .
Improvement of alveolar glutathione and lung function but not oxidative state in cystic
fibrosis.
Am J Respir Crit Care Med.
2004;
169
822-888
Reference Ris Wihthout Link
- 61
Griese M, Latzin P, Kappler M. et al .
Alpha1 Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients.
Eur Respir J.
2007;
29
240-250
Reference Ris Wihthout Link
- 62 Köhler D, Fleischer W. Medikamente. In: Theorie und Praxis der Inhalationstherapie. Köhler D, W. Fleischer (Eds.). Arcis Verlag 2000: 71-99
Reference Ris Wihthout Link
- 63
Gonda I.
Systemic delivery of drugs to humans via inhalation.
J Aerosol Med.
2006;
19
47-53
Reference Ris Wihthout Link
- 64
Siekmeier R, Scheuch G.
Systemische Therapie mit Aerosolen: Beispiele zur pulmonalen Verabreichung von Makromolekülen
zur systemischen Therapie.
Atemw.-Lungenkrkh.
2006;
31
391-410
Reference Ris Wihthout Link
- 65
Heubner W, deJongh S E, Laquer E. et al .
Ueber Inhalation von Insulin.
Klin Wochenschr.
1924;
3
2343
Reference Ris Wihthout Link
- 66
Gaenslein M.
Über Inhalation von Insulin.
Klin Wochenschr.
1925;
4
71
Reference Ris Wihthout Link
- 67
Brain J D.
Inhalation, Deposition and Fate of Insulin and other Therapeutic Proteins.
Diabetes Technologies and Therapeutics.
2007;
9
S4-S15
Reference Ris Wihthout Link
- 68
Rosner S W.
Heparin administered as an aerosol.
Vasc Dis.
1965;
125
131-134
Reference Ris Wihthout Link
- 69
Köhler D.
Aerosolized heparin.
J Aerosol Med.
1994;
7
307-314
Reference Ris Wihthout Link
- 70
Scheuch G, Müllinger B, Spannagl M. et al .
Antikoagulation durch kontrollierte Inhalation von Certoparin.
Atemw.-Lungenkrkh.
2005;
31
420-430
Reference Ris Wihthout Link
- 71 Haeussermann S, Brand P, Herpich C. et al .The inhalation of low molecular weight heparin for systemic anti-coagulative action. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ. (Eds.), Respiratory Drug Delivery
VIII. Davis Healthcare Int. Publ.: River Grove, IL 633-637
Reference Ris Wihthout Link
1 Prof. Dr. Dieter Köhler zum 60. Geburtstag gewidmet.
Dr. Peter Haidl
Fachkrankenhaus Kloster Grafschaft, Abteilung Pneumologie II
Annostr. 1
57392 Schmallenberg
Email: p.haidl@t-online.de