Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

Kioumis, Ioannis; Lampaki, Sofia; Organtzis, John; Porpodis, Κonstantinos; Spyratos, Dionysios; Pitsiou, Georgia; Petridis, D.; Pataka, Athanasia; Huang, Haidong; Li, Qiang; Yarmus, Lonny; Hohenforst-Schmidt, Wolfgang; Pezirkianidis, Nikolaos; Zarogoulidis, Konstantinos

doi:10.2147/dddt.s66576

Cited by 8 publications

(7 citation statements)

References 39 publications

(40 reference statements)

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“…12, 13 This route of administration delivers a high concentration of drug to the lungs, while simultaneously bypassing the high systemic load needed to push drug concentrations to therapeutic levels in pulmonary tissues. Currently, this delivery method is accomplished by wet nebulization, which forms fine aerosol droplets of drug in-line with the ventilator for forced ventilator inhalation; however, the only option for pulmonary delivery of vancomycin is to administer a nebulized vancomycin that is only formulated and approved for IV use.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits

et al. 2015

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Antibiotic multi-resistant pneumonia is a risk associated with long term mechanical ventilation. Vancomycin is commonly prescribed for methicillin-resistant staphylococcus aureus infections; however, current formulations of vancomycin are only given intravenously. High doses of vancomycin have been associated with severe renal toxicity. In this study we characterized dry powder vancomyin as a potential inhaled therapeutic aerosol and compared pharmacokinetic profiles of i.v. and pulmonary administered vancomycin in intubated rabbits using a novel endotracheal tube catheter system. Cascade Impaction studies indicated that using an endotracheal tube, which bypasses deposition the mouth and throat, increased the amount of drug entering the lung. Drug deposition in the lung was further enhanced by using an endotracheal tube catheter, which did not alter the aerosol fine particle fraction. Interestingly, intubated rabbits administered 1 mg/kg vancomycin via inhalation had similar AUC to rabbits that were administered 1 mg/kg vancomycin via a single bolus i.v. infusion; however, inhalation of vancomycin reduced Cmax and increased Tmax, suggesting that inhaled vancomycin resulted in more sustained pulmonary levels of vancomycin. Collectively, these results suggested that dry powder vancomycin can successfully be delivered by pulmonary inhalation in intubated patients. Furthermore, as inhaled vancomycin is delivered locally to the site of pulmonary infection, this delivery route could reduce the total dose required for therapeutic efficacy and simultaneously reduce the risk of renal toxicity by eliminating the high levels of systemic drug exposure required to push the pulmonary dose to therapeutic thresholds during i.v. administration.

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Section: Introductionmentioning

confidence: 99%

Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits

et al. 2015

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“…The major adverse effects were cough, dysgeusia, dysphonia, bronchospasm, pharyngitis, pneumothorax, tinnitus wheezing and hoarseness of voice. In the experiments by Zarogoulidis P. et al [9,48] with ampicillin-sulbactam, meropenem, ceftazidime, cefepime, piperacillin-tazobactam, linezolid, vancomycin and daptomycin it was observed that again the residual cup design along with specific jet-nebulizer compressor parameters were the most important factors affecting the small droplet production.…”

Section: Antibioticsmentioning

confidence: 98%

Drug development of Lung Diseases by way of Drug Repurposing; What a Pulmonary Physician can do in the Laboratory

Tsiouda¹,

Hohenforst-Schmidt²,

Sardeli³

et al. 2018

J. Biomed

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Lung diseases are very common among several patients such as; asthma, chronic obstructive pulmonary disease, lung cancer, cystic fibrosis and pulmonary fibrosis. In many of these diseases we already have inhalation therapies, however; for others we have only systematic administration. There are also diseases of the lung that cause pulmonary hypertension and architectural damage to the lung such as; emphysema and bronchiectasis. Several of the drugs currently administered intravenously are being investigated whether they could be transformed and delivered as aerosol therapy. We will present the methodology that can be used and has been used for several drugs.

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“…In the TRIUMPH trial treprostinil provided data where the 6-minute walking test was improved when compared to stable doses of bonsentan or sildenafil alone [15]. It has been previously investigated that different types and models of nebulisers in combination with different residual cup design and fillings affect the size of the aerosol production size [4,16,17]. The aim of this experiment was to investigate the possible administration of these drugs as aerosols and which would be the best equipment combination and residual cup filling.…”

Section: Introductionmentioning

confidence: 99%

Modification Tadalafil and Macitentan tablets to aerosol

Petridis¹,

Sardeli²,

Kosmıdis³

et al. 2022

Front. Biosci. (Landmark Ed)

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Introduction: Aerosolised drugs have been approved for several diseases such as cystic fibrosis and diabetes. Moreover; there are already drugs for pulmonary hypertension in aerosol form already on the market. Materials and methods: Two drugs for pulmonary hypertension (Tadalafil and Macitentan) were milled and transformed from tablets to powder. Three different jet-nebulizers with seven different residual cups were combined. Moreover, we used 3 different ultrasound nebulizers with two different release methods. Results: The drug and residual cup designs produce alone or jointly different MMAD diameters. The three large (10 mls) residual cups with the jet-nebulisers produced the smallest aerosol droplets. Both ultrasound nebulisers are capable of producing optimal size aerosol droplets ≤5 µm mmad. Conclusions: These two drugs can be easily administered as aerosol and an vivo clinical study will prove the safety for the airways.

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Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

Cited by 8 publications

References 39 publications

Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits

Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits

Drug development of Lung Diseases by way of Drug Repurposing; What a Pulmonary Physician can do in the Laboratory

Modification Tadalafil and Macitentan tablets to aerosol

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