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 in the airway surface liquid (ASL) lining tracheobronchial airways. METHODS:Established models of regional deposition and ASL volumes were used to provide input to a new model evaluating the disposition of drug resulting from dissolution or release, absorption, and mucociliary clearance. Additional modeling of oral absorption, distribution, and elimination allowed prediction of systemic exposure. Herein, predicted ASL and plasma concentrations of free (dissolved or unencapsulated) ciprofloxacin over time are reported for a healthy, adult lung model following inhalation of single doses of nebulized liposomal (6 mL of liposomal ciprofloxacin for inhalation, 50 mg/mL, or 6 mL of Pulmaquin, 210 mg; Aradigm) and dry powder (32.5 and 65 mg doses; Bayer) formulations. RESULTS:Over a range of mucous production rates and tracheal clearance velocities, peak ASL concentrations of free ciprofloxacin were consistently greater for Pulmaquin than for other formulations investigated, owing to the presence of free drug in the nebulized Pulmaquin formulation. The time that ASL concentrations of free drug remained above the minimum inhibitory concentration for Pseudomonas aeruginosa was similar for all four formulations. Predicted plasma ciprofloxacin concentration profiles were in good agreement with available data from Phase I trials in healthy volunteers. CONCLUSIONS:Predictions of ASL drug concentrations over time are valuable in elucidating the roles of deposition, drug release or dissolution, and disposition on the effectiveness of inhaled aerosol therapies. For inhaled ciprofloxacin, the present results predict similar ASL concentrations of free drug over time following single doses of inhaled liposomal and dry powder formulations. The impact of multiple doses and airway disease warrants further consideration.
journal_name
J Aerosol Med Pulm Drug Delivjournal_title
Journal of aerosol medicine and pulmonary drug deliveryauthors
Martin AR,Finlay WHdoi
10.1089/jamp.2017.1377subject
Has Abstractpub_date
2018-02-01 00:00:00pages
49-60issue
1eissn
1941-2711issn
1941-2703journal_volume
31pub_type
杂志文章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: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: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: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
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:High flow nasal cannula oxygen therapy (HFT) is increasingly used in intensive and emergency care departments. Patients suffering from respiratory failure, who are likely to benefit from HFT, may require aerosolized bronchodilators; therefore, combining nebulization with HFT may be relevant. This study aimed...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1219
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:Small rodents continue to be the mainstay for the assessment of pharmacological and toxicological data of inhaled therapeutics. For meaningful interpretation of the results information about deposition of aerosol particles in the respiratory tract is warranted, but not trivial to obtain for animals with nose...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2011.0902
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Programmed cell death 4 (PDCD4), a protein that binds to eukaryotic initiation factor 4A (eIF4A), inhibits the initiation of translation. Although a number of tumor suppressors target transcription, Pdcd4 is the first suppressor targeting protein translation, and has also been suggested to function as a tumo...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2009.0778
更新日期:2010-10-01 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::Antibiotic-resistant bacterial infections have renewed interest in finding substitute methods of treatment. The purpose of the present in vitro study was to investigate the possibility of respiratory delivery of a Burkholderia cepacia complex (BCC) bacteriophage by nebulized aerosol administration. Bacteriophages in i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0701
更新日期:2008-12-01 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:Dyspnea significantly impacts quality of life and is one of the most common symptoms in advanced illness. Systemically-administered opioids and benzodiazepines have been the most studied and utilized pharmacologic treatments for refractory dyspnea. Less attention has been given to the use of these medication...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2014.1136
更新日期:2015-02-01 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: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: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: 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
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:The Respimat Soft Mist Inhaler is reported to generate an aerosol with low spray momentum and a small droplet size. However, the transport characteristics of the Respimat aerosol are not well understood. The objective of this study was to characterize the transport and deposition of an aerosol emitted from t...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0708
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Inhaled alpha1-antitrypsin (AAT) is being developed for treatment of cystic fibrosis to protect the lungs from excessive free elastase. High drug costs mandate a very efficient aerosol system to deliver a high payload to the airways. The I-neb Adaptive Aerosol Delivery (AAD) System is a portable, electronic,...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2009.0793
更新日期:2010-04-01 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: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:Use of a valved holding chamber (VHC) in conjunction with a pressurized metered dose inhaler (pMDI) can reduce issues relating to poor actuation-inhalation coordination and potentially improve the lung deposition of aerosol, compared with use of a pMDI alone. However, the performance of a VHC is influenced b...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2013.1067
更新日期:2014-08-01 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::The available toxicity data of benzalkonium chloride (BKC) clearly shows that it is toxic; however, the weight of evidence favors the view that at doses encountered in nasally and orally inhaled pharmaceutical preparations it is well tolerated. The adverse toxicological data predominantly come from in vitro and animal...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2017.1390
更新日期:2018-02-01 00:00:00
abstract::The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. Similarly, the toxicity of environmental and industrial particulate matter is affected not only by the nature of the dust but also by the am...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.29029.cd
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and T...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1216
更新日期:2015-10-01 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::Exhaled breath condensate (EBC) consists mainly of water, but also contains semivolatile and nonvolatile compounds. The aim of this study was to develop a system in which two condensers are simultaneously used in series to clarify the mechanisms of EBC condensation. Two aliquots of EBC (EBC1 and EBC2) were collected f...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2007.0644
更新日期:2008-03-01 00:00:00
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: Inhalation of medications is the cornerstone in the treatment of patients with lung diseases. A variety of inhalation devices exists and each device has specific requirements to achieve optimum inhalation of the drug. The goal of this study was to establish a c...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1376
更新日期:2018-12-01 00:00:00
abstract::Flexhaler is a multiple-dose, inspiratory flow-driven dry powder inhaler that is a newer version of Turbuhaler, and is identical to the Symbicort Turbuhaler. Sustained performance is of the utmost importance to ensure consistent drug delivery throughout the lifespan of the inhaler. We report functionality testing resu...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0700
更新日期:2008-12-01 00:00:00