A randomized placebo-controlled study of nebulized liposomal amikacin (Arikace™) in the treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

Dupont, Lieven; Minić, Predrag; Fustic, S.; Mazurek, Henryk; Sólyom, Enikő; Feketova, A.; Csiszér, Eszter; Gupta, Renu

doi:10.1016/s1569-1993(08)60099-5

Cited by 22 publications

(3 citation statements)

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“…These findings are in agreement with findings of other clinical tobramycin studies (164,209,210). Aerosolized administration of liposomal amikacin to CF patients did not result in a PK/PD-driven change in lung function tests, but a concentration-dependent reduction of bacterial load was correlated to the AUC/MIC ratio (170,171,222).…”

Section: Preclinical and Clinical Pk/pd Studies In Cf Patientsmentioning

confidence: 89%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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Section: Preclinical and Clinical Pk/pd Studies In Cf Patientsmentioning

confidence: 89%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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“…26 Faz 2 çalışmalarda 280 ve 560 mg (Arikace ® ) olarak 28 gün kullanıldığında balgamda yüksek konsantrasyonda saptanmış ve güvenli bulunmuştır. 27 Mukolitikler ve mukus hareketlendiriciler Dornaz alfa (Rekombinant insan DNase): İnsan DNase I enziminin rekombinant formudur. KF hastalarının mukusundaki nekroza uğramış nötrofillerden açığa çıkan çok miktardaki serbest DNA'yı yıkarak solunum yolu sekresyonlarının viskoelastisitesini azaltır ve mukusun klirensini artırır.…”

Section: Tanı Amacıylaunclassified

Inhaled Therapy in Children

Pekcan¹

2012

Solunum

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“…The potential of nanocarriers for lung disease was first illustrated clinically with nebulization (inhaled aerosol) of the antibiotic amikacin loaded into liposomes (Arikyace). [ 9 , 10 ] Arikyace gained FDA approval in 2018 for improving the treatment of nontuberculous mycobacteria, which primarily infects the airways. [ 11 ] While this represents yet another triumph of therapy for diseases of the airways rather than the alveoli, it also suggests that alveolar diseases might similarly benefit from nanocarriers.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases

Ferguson

Myerson

et al. 2023

Advanced NanoBiomed Research

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Diseases of the pulmonary alveolus, such as pulmonary fibrosis, are leading causes of morbidity and mortality, but exceedingly few drugs are developed for them. A major reason for this gap is that after inhalation, drugs are quickly whisked away from alveoli due to their high perfusion. To solve this problem, the mechanisms by which nano‐scale drug carriers dramatically improve lung pharmacokinetics using an inhalable liposome formulation containing nintedanib, an antifibrotic for pulmonary fibrosis, are studied. Direct instillation of liposomes in murine lung increases nintedanib's total lung delivery over time by 8000‐fold and lung half life by tenfold, compared to oral nintedanib. Counterintuitively, it is shown that pulmonary surfactant neither lyses nor aggregates the liposomes. Instead, each lung compartment (alveolar fluid, alveolar leukocytes, and parenchyma) elutes liposomes over 24 h, likely serving as “drug depots.” After deposition in the surfactant layer, liposomes are transferred over 3–6 h to alveolar leukocytes (which take up a surprisingly minor 1–5% of total lung dose instilled) in a nonsaturable fashion. Further, all cell layers of the lung parenchyma take up liposomes. These and other mechanisms elucidated here should guide engineering of future inhaled nanomedicine for alveolar diseases.

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A randomized placebo-controlled study of nebulized liposomal amikacin (Arikace™) in the treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

Cited by 22 publications

References 0 publications

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Inhaled Therapy in Children

Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases

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