Abstract:
BACKGROUND:Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). METHODS:The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. RESULTS:A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. CONCLUSIONS:Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.
journal_name
J Aerosol Med Pulm Drug Delivjournal_title
Journal of aerosol medicine and pulmonary drug deliveryauthors
Corcoran TE,Venkataramanan R,Hoffman RM,George MP,Petrov A,Richards T,Zhang S,Choi J,Gao YY,Oakum CD,Cook RO,Donahoe Mdoi
10.1089/jamp.2011.0948subject
Has Abstractpub_date
2013-02-01 00:00:00pages
46-55issue
1eissn
1941-2711issn
1941-2703journal_volume
26pub_type
杂志文章,随机对照试验abstract:BACKGROUND:The site of deposition in the respiratory tract for aerosolized, inhaled therapeutic drugs depends on both the particles' aerodynamic size and the patient's breathing pattern. METHODS:In 21 healthy subjects with normal lung function, we evaluated an extremely slow inhalation of a large 9.5-μm MMAD particle ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0711
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:Particle size and velocity are two of the most significant factors that impact the deposition of pressurized metered-dose inhaler (pMDI) sprays in the mouth cavity. pMDIs are prominently used around the world in the treatment of patients suffering from a variety of lung diseases such as asthma and chronic ob...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1264
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abstract::Significant advances have been made in the last 50 years in developing safe and efficacious aerosol formulations for pulmonary delivery. The key to future innovation may lie at the interface between biology and particle engineering. Improved understanding of biological processes including particle clearance, cellular ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2010.0838
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abstract:BACKGROUND:Very little is known about the role of nasal morphology due to ethnic variation on particle deposition pattern in the sinonasal cavity. This preliminary study utilizes computational fluid dynamics (CFD) modeling to investigate sinonasal airway morphology and deposition patterns of intranasal sprayed particle...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1205
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abstract:: Background: Many countries have introduced a compulsory use of community masks for certain public areas during the SARS-CoV-2 pandemic. Different manufacturers offer reusable community masks in large quantities. The efficacy of these masks, however, is unknown. ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
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doi:10.1089/jamp.2020.1635
更新日期:2020-09-23 00:00:00
abstract::This article provides a concise review of the use of magnetic resonance imaging (MRI) for measurement of regional aerosol deposition in the lungs. Basic aspects of MRI and its use in lung imaging and measurement of regional ventilation are introduced. Imaging of hydrogen protons (water) and inhaled hyperpolarized gase...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0897
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abstract:BACKGROUND:Understanding the regional partition of deposition of inhaled particles within the lung is important for improving targeted delivery of inhaled aerosolized drugs. One factor affecting regional deposition is gravity. As the lung deforms under its own weight, changes in lung volume, in airway geometries, and i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1189
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Computer modeling is used to predict inhaled aerosol deposition in the lung based on definition of the aerosol characteristics and the breathing pattern and airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three-dimensional imaging provides an oppo...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1191
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Preclinical evaluation of new chemical entities (NCEs) designed to be administered by inhalation route requires lung administration to rodents, especially in the discovery phase. Different administration methods have been used until now, but more efforts are required to obtain controlled and reproducible lun...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
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doi:10.1089/jamp.2017.1369
更新日期:2018-02-01 00:00:00
abstract::Since the early 1960s, there has been a continuous evolution in scientific understanding regarding bioequivalence (BE) of oral dosage forms, intermittently punctuated by some breakthrough research findings and conceptual advances. The accumulated knowledge from this body of research has been translated into a sophisti...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2014.1144
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abstract:BACKGROUND:Remote inhaler monitoring is an emerging technology that enables the healthcare team to monitor the time and location of a patient's inhaler use. We assessed the feasibility of remote inhaler monitoring for chronic obstructive pulmonary disease (COPD) patients and the pattern of albuterol inhaler use associa...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1383
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Inhaled corticosteroid (ICS) therapy has improved the quality of life (QOL) for many asthmatics and reduced mortality rates associated with asthma. However, some patients do not obtain therapeutic benefit despite satisfactory adherence. OBJECTIVES:To determine whether asthmatic patients were using ICS devic...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2010.0868
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol in...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2016.1320
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Model predictions of regional deposition in the respiratory tract are useful in assessing factors that influence the effectiveness of aerosol delivery. Regional deposition models have previously been coupled with models of mucous production and clearance to estimate initial concentrations of drug deposited i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1377
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:Secondary lung infections are the primary cause of morbidity associated with cystic fibrosis lung disease. Aerosolized antibiotic inhalation is potentially advantageous but has limited effectiveness due to altered airway aerodynamics and deposition patterns that limit drug access to infected regions. One pot...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1412
更新日期:2018-08-01 00:00:00
abstract:: Background: Many substances used in inhalation research are water soluble and can be administered as nebulized solutions. Typical examples are therapeutic, small-molecular agents, or macromolecules. Another category is a number of water-soluble agents used for airway diagn...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2019.1554
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition. METHODS:An abbreviated impactor base...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2011.0925
更新日期:2012-08-01 00:00:00
abstract:: Background: Salvia miltiorrhiza polyphenolic acid (SMPA) is effective in the treatment of cardiovascular diseases and currently it is administered orally or intravenously. However, SMPA is poorly absorbed orally and quickly eliminated in vivo. A long-term frequent intraveno...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2019.1538
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which doe...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1208
更新日期:2015-12-01 00:00:00
abstract::The use of gamma camera imaging following the inhalation of a radiolabel has been widely used by researchers to investigate the fate of inhaled aerosols. The application of two-dimensional (2D) planar gamma scintigraphy and single-photon emission computed tomography (SPECT) to the study of inhaled aerosols is discusse...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0960
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1438
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVES:This experimental study was conducted to determine the effects of training on inhaler technique and quality of life in patients with chronic obstructive pulmonary disease (COPD). METHODS:Among the patients who applied at the outpatient clinic of chest diseases between March 2009 and May 2010, a total of 69 ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,随机对照试验
doi:10.1089/jamp.2012.1017
更新日期:2013-12-01 00:00:00
abstract::The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were rec...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,随机对照试验
doi:10.1089/jamp.2008.0690
更新日期:2008-09-01 00:00:00
abstract::Upper respiratory tract infections (URTIs), primarily acute rhinopharyngitis, tonsillitis, adenoiditis, and rhinosinusitis (RS), are major causes of morbidity in both children and adults of any age. In addition to the frequent occurrence of related medical problems and the associated socioeconomic costs, URTIs have a ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2016.1300
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:The delivery of antitubercular drugs through direct lung targeting can lead to reduction in the dose as well as side effects of the drug. In the present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin was prepared to achieve direct targeting of the drug into the lungs. METHODS:The dr...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1379
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:Many methods have been developed to evaluate dry powder inhalation techniques and their efficiency for disease control in asthma patients. However, it is difficult to apply these methods to clinical practice and research. In this study, we introduce a simple new method that can be applied to dry powder inhalati...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1193
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Predicting local lung tissue pharmacodynamic (PD) responses of inhaled drugs is a longstanding challenge related to the lack of experimental techniques to determine local free drug concentrations. This has prompted the use of physiologically based pharmacokinetic (PBPK) modeling to potentially predict local ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1436
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Researchers, using checklists, have identified that 30%-90% of patients make errors in inhaler use. It is not certain whether these errors affect the delivery of medication. We have developed an electronic monitor (INCA™) that records audio each time an inhaler is used, providing objective information on inh...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2016.1334
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:To validate the 'Test of Adherence to Inhalers' (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma. METHODS:A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study. Patients with electronic adherence ≥80% were ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,多中心研究
doi:10.1089/jamp.2015.1212
更新日期:2016-04-01 00:00:00
abstract:: Background: The photo reflection method (PRM) is used to measure light reflected from particles released from dry powder inhalers (DPIs). This simple method depicts time trajectories of released drugs; however, it underestimates the number of particles at high peak inhalat...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.1610
更新日期:2020-11-04 00:00:00