Inhalation of tobramycin using simulated cystic fibrosis patient profiles

Haynes, Alfred; Geller, David E.; Weers, Jeffry G.; Ament, Brian; Pavkov, Richard; Malcolmson, Richard; DeBonnett, Laurie; Mastoridis, Paul; Yadao, Anthony

doi:10.1002/ppul.23451

Cited by 38 publications

(32 citation statements)

References 35 publications

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“…This is particularly the case with high-dose inhalers such as the Tobi Podhaler (112 mg tobramycin/dose), which may require two inhalations to ensure patients adequately extract the full dose from each of the four capsules. (66) However, it should be noted that the inhaled volume required to extract the dose from most inhalers is more than achievable by patients of all ages and disease severities.…”

Section: Other Parameters That Can Influence Dpi Performancementioning

confidence: 99%

The Confusing World of Dry Powder Inhalers: It Is All About Inspiratory Pressures, Not Inspiratory Flow Rates

Clark¹,

Weers²,

Dhand

2020

Journal of Aerosol Medicine and Pulmonary Drug Delivery

105

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Dry powder inhalers (DPIs) all have the ability to aerosolize dry powders, but they each offer different operating mechanisms and resistances to inhaled airflow. This variety has resulted in both clinician and patient confusion concerning DPI performance, use, and effectiveness. Particularly, there is a growing misconception that a single peak inspiratory flow rate (PIFR) can determine a patient's ability to use a DPI effectively, regardless of its design or airflow resistance. For this review article, we have sifted through the relevant literature concerning DPIs, inspiratory pressures, and inspiratory flow rates to provide a comprehensive and concise discussion and recommendations for DPI use. We ultimately clarify that the controlling parameter for DPI performance is not the PIFR but the negative pressure generated by the patient's inspiratory effort. A pressure drop * ‡1 kPa (*10 cm H 2 O) with any DPI is a reasonable threshold above which a patient should receive an adequate lung dose. Overall, we explore the underlying factors controlling inspiratory pressures, flow rates and dispensing, and dispersion characteristics of the various DPIs to clarify that inspiratory pressures, not flow rates, limit and control a patient's ability to generate sufficient flow for effective DPI use.

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Section: Other Parameters That Can Influence Dpi Performancementioning

confidence: 99%

The Confusing World of Dry Powder Inhalers: It Is All About Inspiratory Pressures, Not Inspiratory Flow Rates

Clark¹,

Weers²,

Dhand

2020

Journal of Aerosol Medicine and Pulmonary Drug Delivery

105

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“…In the last decade, numerous phospholipidbased formulations have been advanced into the clinic for the pulmonary administration of anti-infectives. These include two formulations that have achieved marketing authorization: TOBI Ò Podhaler TM , a spray-dried dry powder formulation of tobramycin sulfate for the treatment of chronic Pseudomonas aeruginosa infections in cystic fibrosis (CF) patients [1][2][3][4][5], and Arikayce Ò , a liposomal dispersion of amikacin sulfate for the treatment of non-tuberculosis mycobacterial (NTM) infections [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Phospholipid-Based Particles for Sustained Release of Ciprofloxacin Following Pulmonary Administration to Bronchiectasis Patients

Weers¹

2019

Pulm Ther

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The rapid clearance of ciprofloxacin hydrochloride from the lungs following administration as an aerosol leads to poor efficacy in the treatment of pulmonary infections. The development of formulations capable of sustaining ciprofloxacin concentrations in the lungs has the potential to significantly improve antibacterial activity. The present review compares two approaches for sustaining levels of ciprofloxacin in the lungs, a liposomal formulation where ciprofloxacin is encapsulated in small unilamellar vesicles, and a dry powder formulation of the practically insoluble zwitterionic form of the drug. These two formulations recently completed large multicenter, phase 3 clinical studies in bronchiectasis patients. As such, they present a unique opportunity to examine the chemistry, manufacturing, and control of the dosage forms in addition to their tolerability and efficacy in more than 1000 bronchiectasis patients. Both formulations were generally well tolerated with most adverse events found to be mild to moderate in intensity. While the formulations were effective in reducing and/or eradicating infections, this did not lead to reductions in pulmonary exacerbations, the primary endpoint. The failures speak more to the heterogeneous nature of the disease and the difficulty in identifying bronchiectasis patients likely to exacerbate, rather than an inherent limitation of the formulations. While the formulations are similar in many respects, they also present some interesting differences. This review explores the implications of these differences on the treatment of respiratory infections.

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“…Second, TIP particles might hit the throat wall with greater impact, due to the relatively faster inhalation of TIP compared to TIS. The T‐326 inhaler has a low‐to‐medium resistance (approximately 0.08 [cm H 2 O] ½ /[L/min]), fast inspiratory flows between 40 up to 115 L/min were observed in a laboratory setting when inhaling TIP . On the contrary, TIS is inhaled with tidal volume breathing.…”

Section: Introductionmentioning

confidence: 99%

“…This might be a result of higher upper airway deposition. Importantly, according to an in vitro study by Haynes et al, the total lung dose of TIP is independent of inspiratory flow.…”

Section: Introductionmentioning

confidence: 99%

“…The T-326 inhaler has a low-to-medium resistance (approximately 0.08 [cm H 2 O] ½ /[L/min]), fast inspiratory flows between 40 up to 115 L/min were observed in a laboratory setting when inhaling TIP. 11 On the contrary, TIS is inhaled with tidal volume breathing. Third, tobramycin sputum concentrations were found to be double after inhalation of TIP compared to that of TIS.…”

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confidence: 99%

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Home videos of cystic fibrosis patients using tobramycin inhalation powder: Relation of flow and cough

Meerburg

Albasri

Wiel

et al. 2019

Pediatric Pulmonology

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BackgroundMany cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa are on maintenance tobramycin inhalation therapy. Cough is reported as a side effect of tobramycin inhalation powder (TIP) in 48% of the patients. Objectives of this study were to investigate the association between the inspiratory flow of TIP and cough and to study the inhalation technique. We hypothesized that cough is related to a fast inhalation.Materials and MethodsIn this prospective observational study, CF patients ≥ 6 years old on TIP maintenance therapy from four Dutch CF centers were visited twice at home. Video recordings were obtained and peak inspiratory flow (PIF) was recorded while patients inhaled TIP. Between the two home visits, the patients made three additional videos. CF questionnaire‐revised, spirometry data, and computed tomography scan were collected. Two observers scored the videos for PIF, cough, and mistakes in inhalation technique. The associations between PIF and cough were analyzed using a logistic mixed‐effects model accounting for FEV1% predicted and capsule number.ResultsTwenty patients were included, median age 22 (18–28) years. No significant associations were found between PIF and cough. The risk of cough was highest after inhalation of the first capsule when compared to the second, third, and fourth capsule (P ≤ .015). Fourteen patients (70%) coughed at least once during TIP inhalation. A breath‐hold of less than 5 seconds after inhalation and no deep expiration before inhalation were the most commonly observed mistakes.ConclusionPIF is not related to cough in CF patients using TIP.

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Inhalation of tobramycin using simulated cystic fibrosis patient profiles

Cited by 38 publications

References 35 publications

The Confusing World of Dry Powder Inhalers: It Is All About Inspiratory Pressures, Not Inspiratory Flow Rates

The Confusing World of Dry Powder Inhalers: It Is All About Inspiratory Pressures, Not Inspiratory Flow Rates

Comparison of Phospholipid-Based Particles for Sustained Release of Ciprofloxacin Following Pulmonary Administration to Bronchiectasis Patients

Home videos of cystic fibrosis patients using tobramycin inhalation powder: Relation of flow and cough

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