Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"<i>In Vitro</i> Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler.","authors":"Melanie Hamilton,&nbsp;Martin Anderson,&nbsp;Rajiv Dhand,&nbsp;Oonagh Patmore,&nbsp;David Prime,&nbsp;Edward Taylor","doi":"10.1089/jamp.2021.0061","DOIUrl":"https://doi.org/10.1089/jamp.2021.0061","url":null,"abstract":"<p><p><b><i>Background:</i></b> Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. <b><i>Materials and Methods:</i></b> The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg and FF/UMEC/VI 200/62.5/25 μg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. <b><i>Results:</i></b> During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 μg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 μg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 μm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. <b><i>Conclusions:</i></b> Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"34-43"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Single Photon Emission Computed Tomography in Aerosol Medicine.","authors":"John S Fleming","doi":"10.1089/jamp.2023.29077.jsf","DOIUrl":"https://doi.org/10.1089/jamp.2023.29077.jsf","url":null,"abstract":"<p><p>Imaging of radiolabeled aerosols provides useful <i>in vivo</i> data on both the initial site of deposition and its subsequent transport by mucociliary clearance and epithelial permeability. Single Photon Emission Computed Tomography (SPECT) uses a gamma camera with multiple rotating heads to produce three-dimensional (3D) images of inhaled radioaerosol labeled with technetium-99m. This enables total lung deposition and its 3D regional distribution to be quantified. Aligned 3D images of lung structure allow deposition data to be related to lung anatomy. Mucociliary clearance or epithelial permeability can be assessed from a time series of SPECT aerosol images. SPECT is slightly superior to planar imaging for measuring total lung deposition. However, it is more complex to use, and for studies where total lung deposition is the endpoint, planar imaging is recommended. However, SPECT has been shown to be clearly superior to planar imaging for assessing regional distribution of aerosol and is the method of choice for this purpose. It therefore has applications in studying the influence of regional deposition on clinical effectiveness and also in validating computer models of deposition. The inability to directly radiolabel drug molecules with ^99mTc is a clear disadvantage of SPECT and limits its potential use for pharmacokinetic studies. SPECT provides a wealth of data on aerosol deposition, which has been relatively underused at present. Optimal methods of analyzing and interpreting the data need to be developed. SPECT can also, in principle, provide detailed information of mucociliary clearance and has the potential to significantly improve knowledge of this process and hence clarify the role of clearance as a biomarker.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"44-53"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9591838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Investigation into the Factors Associated with Incorrect Use of a Pressurized Metered-Dose Inhaler in Japanese Patients.","authors":"Hiroshi Ohnishi,&nbsp;Masafumi Okazaki,&nbsp;Kazuki Anabuki,&nbsp;Shin Akita,&nbsp;Shigeo Kawase,&nbsp;Kimiko Sakai Tsuji,&nbsp;Mitsuhiko Miyamura,&nbsp;Akihito Yokoyama","doi":"10.1089/jamp.2022.0018","DOIUrl":"https://doi.org/10.1089/jamp.2022.0018","url":null,"abstract":"<p><p><b><i>Rationale:</i></b> Inhalation of the correct dose of a short-acting beta 2 agonist (SABA) from a pressurized metered-dose inhaler (pMDI) is essential for the relief of symptoms in patients with asthma and/or chronic obstructive pulmonary disease. The aim of this study was to evaluate the prevalence and factors associated with the incorrect use of a pMDI. <b><i>Methods:</i></b> This study retrospectively assessed the electronic medical records of 161 patients with various respiratory diseases. The patients had never used a pMDI and underwent training by pharmacists educated in the use of a pMDI followed by bronchodilator reversibility testing at our hospital. The patients' characteristics and various lung capacity parameters were evaluated for association with the incorrect use of a pMDI. <b><i>Results:</i></b> Thirty-nine of the 161 (24.2%) patients, including 46% of 28 patients older than 80 years, used the pMDI incorrectly, mainly because of incoordination between activation of the device and inhalation (<i>n</i> = 11), inadequate strength to manipulate the device (<i>n</i> = 9), too short duration of inhalation (<i>n</i> = 6), and difficulty in breath holding (<i>n</i> = 3). Advanced age; lower height; and decreased lung volumes, including vital capacity (VC), inspiratory capacity, inspiratory reserve volume (IRV), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow rate, were associated with the incorrect use of a pMDI. Neither the body weight, tidal volume, expiratory reserve volume, %FVC predicted, %FEV1 predicted, nor FEV1% was associated with the incorrect use of a pMDI. Multivariate binomial logistic regression analysis identified decreased IRV as the only independent predictor associated with the incorrect use of a pMDI. <b><i>Conclusions:</i></b> Physicians should be aware that elderly patients or patients with decreased IRV might be unable to obtain the correct SABA dose from a pMDI. A large-scale prospective study is required to confirm these findings from our retrospective study with a small group of patients.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"12-19"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9215892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Machine Learning for Segmentation of the Pulmonary Acinus Imaged by Synchrotron X-Ray Tomography.","authors":"Branko Arsic,&nbsp;Igor Saveljic,&nbsp;Frank S Henry,&nbsp;Nenad Filipovic,&nbsp;Akira Tsuda","doi":"10.1089/jamp.2022.0051","DOIUrl":"https://doi.org/10.1089/jamp.2022.0051","url":null,"abstract":"<p><p><b><i>Background:</i></b> To assess the effectiveness of inhalation therapy, it is important to evaluate the lungs' structure; thus, visualization of the entire lungs at the level of the alveoli is necessary. To achieve this goal, the applied visualization technique must satisfy the following two conditions simultaneously: (1) it has to obtain images of the entire lungs, since one part of the lungs is influenced by the other parts, and (2) the images have to capture the detailed structure of the alveolus/acinus in which gas exchange occurs. However, current visualization techniques do not fulfill these two conditions simultaneously. Segmentation is a process in which each pixel of the obtained high-resolution images is simplified (i.e., the representation of an image is changed by categorizing and modifying each pixel) so that we can perform three-dimensional volume rendering. One of the bottlenecks of current approaches is that the accuracy of the segmentation of each image has to be evaluated on the outcome of the process (mainly by an expert). It is a formidable task to evaluate the astronomically large numbers of images that would be required to resolve the entire lungs in high resolution. <b><i>Methods:</i></b> To overcome this challenge, we propose a new approach based on machine learning (ML) techniques for the validation step. <b><i>Results:</i></b> We demonstrate the accuracy of the segmentation process itself by comparison with previously validated images. In this ML approach, to achieve a reasonable accuracy, millions/billions of parameters used for segmentation have to be optimized. This computationally demanding new approach is achievable only due to recent dramatic increases in computation power. <b><i>Conclusion:</i></b> The objective of this article is to explain the advantages of ML over the classical approach for acinar imaging.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"27-33"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/06/jamp.2022.0051.PMC9942171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9222232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2022.","authors":"","doi":"10.1089/jamp.2023.29083.ack","DOIUrl":"https://doi.org/10.1089/jamp.2023.29083.ack","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10485612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Studies of the Nebulized Delivery of Liposomal Amphotericin B.","authors":"Sagar Kothari,&nbsp;Steven G Kefalos,&nbsp;Nicholas D Hages,&nbsp;Timothy E Corcoran,&nbsp;Shahid Husain","doi":"10.1089/jamp.2022.0003","DOIUrl":"https://doi.org/10.1089/jamp.2022.0003","url":null,"abstract":"<p><p><b><i>Background:</i></b> Intravenous liposomal amphotericin B (L-AMB) has accompanying side effects that may be diminished when administering an inhaled form. Delivery systems for inhaled or aerosolized L-AMB vary, and there has not been a recent comparison of available systems to date. <b><i>Methods:</i></b> We compared three differently designed nebulizer delivery systems for the inhaled delivery of L-AMB to determine the best combination of efficient lung dosing and treatment time. Aerosol size was measured using a Malvern Mastersizer, and five separate nebulizers were tested. For drug output measurements, a Harvard Lung was used, and aerosol was collected using HEPA filters. <b><i>Results:</i></b> Overall aerosol size characteristics were similar for all devices with volume median diameters in the 4-5 μm range. The highest inhaled dose was delivered by the AeroEclipse. The Aerogen and the AeroEclipse had similar predicted pulmonary doses, and the AeroEclipse had the highest pulmonary delivery rates. <b><i>Conclusion:</i></b> The AeroEclipse nebulizer may provide more efficient delivery in a shorter amount of time; however, human studies are warranted to assess the safety, tolerability, and efficacy of inhaled delivery of L-AMB from this system.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"307-312"},"PeriodicalIF":3.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10830379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Dose-Response Relationships for Two Isolates of SARS-CoV-2 in a Nonhuman Primate Model of Inhalational COVID-19.","authors":"Paul A Dabisch, Jaleal S Sanjak, Jeremy A Boydston, John Yeager, Artemas Herzog, Jennifer Biryukov, Katie Beck, Danh Do, Brittany G Seman, Brian Green, Jordan K Bohannon, Brian Holland, David Miller, Taylor Ammons, Denise Freeburger, Susan Miller, Tammy Jenkins, Sherry Rippeon, James Miller, David Clarke, Emmanuel Manan, Ashley Patty, Kim Rhodes, Tina Sweeney, Michael Winpigler, Louis A Altamura, Heather Zimmerman, Alec S Hail, Victoria Wahl, Michael Hevey","doi":"10.1089/jamp.2022.0043","DOIUrl":"10.1089/jamp.2022.0043","url":null,"abstract":"<p><p><b><i>Background:</i></b> As the COVID-19 pandemic has progressed, numerous variants of SARS-CoV-2 have arisen, with several displaying increased transmissibility. <b><i>Methods:</i></b> The present study compared dose-response relationships and disease presentation in nonhuman primates infected with aerosols containing an isolate of the Gamma variant of SARS-CoV-2 to the results of our previous study with the earlier WA-1 isolate of SARS-CoV-2. <b><i>Results:</i></b> Disease in Gamma-infected animals was mild, characterized by dose-dependent fever and oronasal shedding of virus. Differences were observed in shedding in the upper respiratory tract between Gamma- and WA-1-infected animals that have the potential to influence disease transmission. Specifically, the estimated median doses for shedding of viral RNA or infectious virus in nasal swabs were approximately 10-fold lower for the Gamma variant than the WA-1 isolate. Given that the median doses for fever were similar, this suggests that there is a greater difference between the median doses for viral shedding and fever for Gamma than for WA-1 and potentially an increased range of doses for Gamma over which asymptomatic shedding and disease transmission are possible. <b><i>Conclusions:</i></b> These results complement those of previous studies, which suggested that differences in exposure dose may help to explain the range of clinical disease presentations observed in individuals with COVID-19, highlighting the importance of public health measures designed to limit exposure dose, such as masking and social distancing. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, as well as to inform dose selection in future studies examining the efficacy of therapeutics and vaccines in animal models of inhalational COVID-19.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"296-306"},"PeriodicalIF":2.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/39/jamp.2022.0043.PMC9807281.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Satisfaction with and Use of Inhalation Devices in Patients with Bronchial Asthma.","authors":"Luis Fernando Valladales-Restrepo,&nbsp;Juan Camilo Saavedra-Navia,&nbsp;Carlos Andrés Montezuma-Casanova,&nbsp;Valentina Montañez-Díaz,&nbsp;Jairo Andrés González-Ospina,&nbsp;Laura Manuela Caballero-Martínez,&nbsp;Andrés Gaviria-Mendoza,&nbsp;Manuel Enrique Machado-Duque,&nbsp;Jorge Enrique Machado-Alba","doi":"10.1089/jamp.2022.0027","DOIUrl":"https://doi.org/10.1089/jamp.2022.0027","url":null,"abstract":"<p><p><b><i>Background:</i></b> Greater patient satisfaction with his or her inhalation device is associated with better adherence to pharmacological therapy and better clinical outcomes, such as improved quality of life, greater asthma control, and fewer exacerbations. The objective of this study was to determine the satisfaction level of a group of patients diagnosed with bronchial asthma concerning their devices for inhalation of bronchodilators and glucocorticoids. <b><i>Methods:</i></b> This was a cross-sectional study of patients treated in the Colombian health system. Satisfaction with inhalation devices was evaluated with the Feeling of Satisfaction with Inhaler (FSI)-10 questionnaire. A score of ≥44 points indicated high satisfaction. <b><i>Results:</i></b> In total, 362 patients from 59 cities were identified, their median age was 55 years, and 74.6% were women. The FSI-10 average score was 44.6; 68.5% of patients showed high satisfaction, especially with pressurized metered-dose inhalers (pMDIs), and 63.4% did not use them with an inhalation chamber. Users of pMDIs (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.05-3.10) and those who received training by medical specialists (OR: 2.29; 95% CI: 1.33-3.97) had high satisfaction, while patients who were older (40-64 vs. <40 years: OR: 0.38; 95% CI: 0.19-0.78 and ≥65 vs. <40 years: OR: 0.35; 95% CI: 0.15-0.81), resided in the Caribbean region (OR: 0.48; 95% CI: 0.29-0.81), and had a university education (OR: 0.54; 95% CI: 0.32-0.90) had lower satisfaction. <b><i>Conclusions:</i></b> The majority of patients with asthma used pMDIs without an inhalation chamber, and their overall satisfaction was higher than that of patients using other inhalation devices. Patients who received special training from medical specialists showed better satisfaction.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"313-320"},"PeriodicalIF":3.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10535143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Pyruvate Nasal Spray Reduces the Severity of Nasal Inflammation and Congestion in Patients with Allergic Rhinitis.","authors":"Alain Martin, Christopher Lupfer, Ronald Amen","doi":"10.1089/jamp.2022.0025","DOIUrl":"10.1089/jamp.2022.0025","url":null,"abstract":"<p><p><b><i>Background:</i></b> As an anti-inflammatory and antioxidant, sodium pyruvate significantly reduces inflammatory cytokines and oxygen radicals such as interleukin (IL) IL-6, IL-8, Monocyte Chemoattractant Protein-1, and hydrogen peroxide. Thus, sodium pyruvate holds promise as a treatment for many respiratory diseases, including allergic rhinitis (AR). Novel treatments for AR are needed as current medications, including steroids, often fail to treat severe symptoms. <b><i>Methods:</i></b> The data from five human clinical studies were analyzed to determine the effect of 20 mM sodium pyruvate nasal spray (N115) in patients with AR. Nasal inflammation scores were compared to a placebo control or a no-treatment baseline control. Three studies were open-labeled and two were appropriately blinded to both patients and clinicians using computer randomization of subjects. <b><i>Results:</i></b> The intranasal administration of sodium pyruvate significantly improved nasal inflammation scores in all five clinical trials of patients with AR (<i>p</i> < 0.0001 in all trials). <b><i>Conclusions:</i></b> These results give credence to the overall ability of sodium pyruvate, administered by nasal spray, to treat inflammation of the nasal airways.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"291-295"},"PeriodicalIF":2.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/0d/jamp.2022.0025.PMC9807276.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of Dihydroergotamine Mesylate to the Upper Nasal Space for the Acute Treatment of Migraine: Technology in Action.","authors":"Wade Cooper,&nbsp;Sutapa Ray,&nbsp;Sheena K Aurora,&nbsp;Stephen B Shrewsbury,&nbsp;Christopher Fuller,&nbsp;Greg Davies,&nbsp;John Hoekman","doi":"10.1089/jamp.2022.0005","DOIUrl":"https://doi.org/10.1089/jamp.2022.0005","url":null,"abstract":"<p><p>Oral tablets account for the majority of medications used to acutely treat migraine, but relief can be limited by their rates of dissolution and absorption. The nose is an attractive alternative route of drug delivery since it provides patient convenience of at-home use, gastrointestinal (GI) avoidance, and rapid absorption of drugs into systemic circulation because of its large surface area. However, the site of drug deposition within the nasal cavity should be considered since it can influence drug absorption. Traditional nasal devices have been shown to target drug delivery to the lower nasal space where epithelium is not best-suited for drug absorption and where there is an increased likelihood of drug clearance due to nasal drip, swallowing, or mucociliary clearance, potentially resulting in variable absorption and suboptimal efficacy. Alternatively, the upper nasal space (UNS) offers a permeable, richly vascularized epithelium with a decreased likelihood of drug loss or clearance due to the anatomy of this area. Traditional nasal pumps deposit <5% of active drug into the UNS because of the nasal cavity's complex architecture. A new technology, Precision Olfactory Delivery (POD^®), is a handheld, manually actuated, propellant-powered, administration device that delivers drug specifically to the UNS. A dihydroergotamine (DHE) mesylate product, INP104, utilizes POD technology to deliver drug to the UNS for the acute treatment of migraine. Results from clinical studies of INP104 demonstrate a favorable pharmacokinetic profile, consistent and predictable dosing, rapid systemic levels known to be effective (similar to other DHE mesylate clinical programs), safety and tolerability on the upper nasal mucosa, and high patient acceptance. POD technology may have the potential to overcome the limitations of traditional nasal delivery systems, while utilizing the nasal delivery benefits of GI tract avoidance, rapid onset, patient convenience, and ease of use.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"321-332"},"PeriodicalIF":3.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10515390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}