Glycopyrrolate/eFlow CS: The First Nebulized Long-Acting Muscarinic Antagonist Approved to Treat Chronic Obstructive Pulmonary Disease

Pleasants, II Roy A.

doi:10.1177/1060028018798753

Cited by 3 publications

(5 citation statements)

References 33 publications

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“…The results of this analysis confirm the nebulization times of approximately 2 min using the eFlowÒ CS nebulizer, independent of breathing patterns assessed, and consistent with previous studies [13,25,32,42]. In addition, the median residual dose of GLY in the nebulizer was markedly lower than that of TIO using the HandiHalerÒ DPI.…”

Section: Discussionsupporting

confidence: 88%

“…DPIs require active, patientdependent airflow generation to draw the powder out of the device and create a disaggregated, breathable aerosol plume that will enter the lungs rather than impact in the mouth and throat [4]. In contrast, drug delivery with a nebulizer is a relatively passive process from the patient's perspective, as the energy required for aerosol generation comes from external sources such as compressed air or a vibrating membrane; it is important to note that nebulization still requires the patient to actively inhale, and thus the process can be considered somewhat active, depending on the nebulizer device and resistance [4,13]. For effective DPI use, patients need to generate sufficient peak inspiratory flow (PIF) to overcome the unique internal resistance of the device in order to disaggregate and disperse the drug [14,15].…”

Section: Introductionmentioning

confidence: 99%

“…Patient characteristics, such as tidal volume, PIF, anatomy of the lungs and inhalation pattern may affect drug deposition in the lower respiratory tract versus the upper airway and oropharyngeal cavity, which impacts treatment efficacy and safety [4][5][6]13]. In addition, aerosol properties such as particle size (assessed by mass median aerodynamic diameter [MMAD]: the diameter at which 50% of the particles by mass are larger and 50% are smaller) affect deposition.…”

Section: Introductionmentioning

confidence: 99%

“…Deposition is also a function of dispersion of particle diameter (assessed by geometric standard deviation [GSD]: the measure of the spread of the aerodynamic particle size distribution) and fine particle levels (assessed by fine particle dose [FPD]: the mass of particles \ 5 lm in size within the total delivered dose; FPF: the FPD, expressed as a percentage of the delivered dose). A GSD C 1.22 is ideal for delivery throughout the lungs; most therapeutic aerosols have a GSD between 2 and 3 [13,20].…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®

Ohar¹,

Bauer²,

Sharma³

et al. 2020

Pulm Ther

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Introduction: Personalized therapy for patients with COPD requires appropriate choice of drug and delivery device. Inhalers and nebulizers vary in their drug delivery characteristics, particularly the need for passive or active patient inhalation for appropriate drug dispersal and delivery. In this in vitro analysis, we assessed the aerosol performance and drug delivery of two long-acting muscarinic antagonists, glycopyrrolate (GLY; 25 lg solution; 1 ml) and tiotropium (TIO; 18 lg powder) through their respective delivery systems: the eFlowÒ Closed System (CS) vibrating membrane nebulizer and the HandiHalerÒ dry-powder inhaler (DPI). Methods: The aerosol performances of the eFlowÒ CS nebulizer and the HandiHalerÒ were determined using the Next Generation cascade Impactor. The delivered dose of GLY and TIO was determined using different breathing patterns, which varied in tidal volume and peak inspiratory flow rate, respectively, to simulate breathing conditions ranging from normal to severe obstruction. Results: Aerodynamic particle analysis showed generally similar mass median aerodynamic diameter (MMAD, range, 3.6-4.6 lm) and fine particle fraction (FPF, range, 48.2%-63.7%) with GLY delivered using the eFlowÒ CS nebulizer under all breathing patterns tested. TIO, delivered via the HandiHalerÒ, showed variations in MMAD (range, 3.8-5.8 lm) and FPF (range, 16.1%-32.4%) under different inspiratory flow rates. The majority of GLY was deposited in stages 2-5 of the impactor, which corresponds with particle sizes in the respirable range (\ 5 lm), whereas a large proportion of TIO was deposited in the throat/mouthpiece pre-separator, irrespective of test conditions. The median residual dose of GLY with eFlowÒ CS was notably lower compared to that of TIO with HandiHalerÒ (2.4%-4.4% vs. 40%-67%, respectively). Conclusions: These simulation results highlight the different deposition patterns generated by a DPI device and a vibrating membrane nebulizer, which may help inform device selection and treatment decision in COPD management.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®

Ohar¹,

Bauer²,

Sharma³

et al. 2020

Pulm Ther

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“…This approval was based on the efficacy and safety demonstrated by the 12-week, replicate, placebo-controlled Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer (GOLDEN) 3 and GOLDEN 4 (NCT02347761 and NCT02347774, respectively), and the 48-week GOLDEN 5 (NCT02276222) phase III randomized clinical trials [ 20 , 21 ]. Magnair ® generates GLY aerosols in the respirable range (1–5 μm) in vitro, allowing efficient pulmonary deposition [ 18 , 22 – 24 ]. The objective of the current study was to characterize the effects of a single dose of nebulized LAMA (GLY 25 μg) on hyperinflation in patients with moderate-to-severe COPD.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Nebulized Glycopyrrolate on Lung Hyperinflation in Patients with COPD

et al. 2021

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Introduction Lung hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with activity limitation, impaired cardiac output, and mortality. Several studies have demonstrated that long-acting muscarinic antagonists (LAMAs) delivered by dry powder inhalers can promote lung deflation; however, the potential of nebulized LAMAs on improving hyperinflation in COPD is currently unknown. Methods This single-center, randomized, double-blind, two-way crossover study (NCT04155047) evaluated the efficacy of a single dose of nebulized LAMA [glycopyrrolate (GLY) 25 µg] versus placebo in patients with COPD and lung hyperinflation. Patients with moderate-to-severe COPD and a residual volume (RV) ≥ 130% of predicted normal were included. The primary endpoint was changed from baseline in RV at 6 h post-treatment. Other endpoints included changes from baseline in spirometric and plethysmographic measures up to 6 h post-treatment. Results A total of 22 patients (mean pre-bronchodilator RV, 153.7% of predicted normal) were included. The primary objective of the study was not met; the placebo-adjusted least squares (LS) mean [95% confidence interval (CI) change from baseline in RV with GLY at 6 h post-treatment was − 0.323 l (− 0.711 to 0.066); p = 0.0987]. A post hoc evaluation of the primary analysis was conducted after excluding a single statistical outlier; substantial improvements in RV with GLY compared with placebo was observed after exclusion of this outlier [placebo-adjusted LS mean change from baseline (95% CI) in RV was − 0.446 l (− 0.741 to − 0.150)]. Improvements from baseline were also observed with GLY compared with placebo in spirometric and plethysmographic measures up to 6 h post-treatment. GLY was generally safe, and no new safety signals were detected. Conclusions This is the first study to evaluate the effect of nebulized GLY on lung deflation. Nebulized GLY resulted in marked improvements in RV up to 6 h post-treatment, compared with placebo. Improvements were also observed with GLY in spirometric and plethysmographic parameters of lung function. Trial Registration ClinicalTrials.gov identifier, NCT04155047. Supplementary Information The online version contains supplementary material available at 10.1007/s41030-021-00166-5.

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Drug Permeability: From the Blood–Brain Barrier to the Peripheral Nerve Barriers

Sun

Zabihi

et al. 2023

Advanced Therapeutics

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Drug delivery into the peripheral nerves and nerve roots has important implications for effective local anesthesia and treatment of peripheral neuropathies and chronic neuropathic pain. Similar to drugs that need to cross the blood–brain barrier (BBB) and blood–spinal cord barrier to gain access to the central nervous system (CNS), drugs must cross the peripheral nerve barriers (PNBs), formed by the perineurium and blood–nerve barrier to modulate peripheral axons. Despite significant progress made to develop effective strategies to enhance BBB permeability in therapeutic drug design, efforts to enhance drug permeability and retention in peripheral nerves and nerve roots are relatively understudied. Guided by knowledge describing structural, molecular, and functional similarities between restrictive neural barriers in the CNS and peripheral nervous system, it is hypothesized that certain CNS drug delivery strategies are adaptable for peripheral nerve drug delivery. Here, the molecular, structural, and functional similarities and differences between the BBB and PNB are described, existing CNS and peripheral nerve drug delivery strategies are summarized and compared, and the potential application of selected CNS delivery strategies to improve efficacious drug entry for peripheral nerve disorders is discussed.

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Glycopyrrolate/eFlow CS: The First Nebulized Long-Acting Muscarinic Antagonist Approved to Treat Chronic Obstructive Pulmonary Disease

Abstract: The recently approved GLY/eFlow CS drug-device combination provides a viable treatment option for patients with COPD, particularly those with conditions that may impair proper use of traditional handheld inhalers.

Cited by 3 publications

References 33 publications

In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®

In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®

Efficacy of Nebulized Glycopyrrolate on Lung Hyperinflation in Patients with COPD

Drug Permeability: From the Blood–Brain Barrier to the Peripheral Nerve Barriers

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