Pulmonary pharmacology & therapeutics最新文献

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The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis 吸入式抗生素治疗肺炎的有效性和安全性:系统回顾与元分析》。
IF 3.3 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-07-14 DOI: 10.1016/j.pupt.2024.102315
Zengzeng Zhang , Hong Li , Yutao Hu , Binhui Sun , Tingting Ke , Qihuan Wu , Xiang Lian , Wei Yu
{"title":"The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis","authors":"Zengzeng Zhang ,&nbsp;Hong Li ,&nbsp;Yutao Hu ,&nbsp;Binhui Sun ,&nbsp;Tingting Ke ,&nbsp;Qihuan Wu ,&nbsp;Xiang Lian ,&nbsp;Wei Yu","doi":"10.1016/j.pupt.2024.102315","DOIUrl":"10.1016/j.pupt.2024.102315","url":null,"abstract":"<div><h3>Objectives</h3><p>The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis.</p></div><div><h3>Methods</h3><p>Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment.</p></div><div><h3>Results</h3><p>There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR) = 1.06, 95 % confidence interval (CI): 0.80–1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR = 1.47 95%CI: 0.82–2.66 in RCT studies and OR = 2.09, 95%CI: 1.36–3.21 in observational studies) and microbiological cure (OR = 7.00 in RCT studies and OR = 2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27–1.13; I-squared = 43.5 %, P = 0.124) and 0.63(95%CI: 0.26–1.11; I-squared = 69.0 %, P = 0.110) in RCT studies and observational studies, respectively.</p></div><div><h3>Conclusions</h3><p>Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102315"},"PeriodicalIF":3.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553924000312/pdfft?md5=5f0cf7dddad61179a42ab1db817fec41&pid=1-s2.0-S1094553924000312-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differential distribution of ivacaftor and its metabolites in plasma and human airway epithelia ivacaftor 及其代谢物在血浆和人体气道上皮细胞中的差异分布。
IF 3.3 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-07-02 DOI: 10.1016/j.pupt.2024.102314
{"title":"Differential distribution of ivacaftor and its metabolites in plasma and human airway epithelia","authors":"","doi":"10.1016/j.pupt.2024.102314","DOIUrl":"10.1016/j.pupt.2024.102314","url":null,"abstract":"<div><p>Ivacaftor is the first clinically approved monotherapy potentiator to treat <em>CFTR</em> channel dysfunction in people with cystic fibrosis. Ivacaftor (Iva) is a critical component for all current modulator therapies, including highly effective modulator therapies. Clinical studies show that CF patients on ivacaftor-containing therapies present various clinical responses, off-target effects, and adverse reactions, which could be related to metabolites of the compound. In this study, we reported the concentrations of Iva and two of its major metabolites (M1-Iva and M6-Iva) in capillary plasma and estimated M1-Iva and M6-Iva metabolic activity via the metabolite parent ratio in capillary plasma over 12 h. We also used the ratio of capillary plasma versus human nasal epithelial cell concentrations to evaluate entry into epithelial cells <em>in vivo</em>. M6-Iva was rarely detected by LC-MS/MS in epithelial cells from participants taking ivacaftor, although it was detected in plasma. To further explore this discrepancy, we performed <em>in vitro</em> studies, which showed that M1-Iva, but not M6-Iva, readily crossed 16HBE cell membranes. Our studies also suggest that metabolism of these compounds is unlikely to occur in airway epithelia despite evidence of expression of metabolism enzymes. Overall, our data provide evidence that there are differences between capillary and cellular concentrations of these compounds that may inform future studies of clinical response and off-target effects.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102314"},"PeriodicalIF":3.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NEK-mediated barrier regulation NEK 介导的屏障调节
IF 3.3 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-06-21 DOI: 10.1016/j.pupt.2024.102313
Nektarios Barabutis
{"title":"NEK-mediated barrier regulation","authors":"Nektarios Barabutis","doi":"10.1016/j.pupt.2024.102313","DOIUrl":"10.1016/j.pupt.2024.102313","url":null,"abstract":"<div><p>Endothelial dysfunction has been associated with devastating outcomes which can eventually lead to permanent disability and death. Elucidation of the meticulously devised network orchestrating endothelial responses, provides information to develop new therapies towards endothelial-related disorders. NEK kinases - which have been involved in the development of human disease – promote vascular leak; suggesting the possibility that their inhibition may ameliorate medical conditions related to barrier derangement.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102313"},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the protective role of sevoflurane in video-assisted thoracoscopic surgery associated-acute lung injury: Inhibition of ferroptosis 揭示七氟醚在视频辅助胸腔镜手术相关急性肺损伤中的保护作用:抑制铁变态反应。
IF 3.3 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-06-19 DOI: 10.1016/j.pupt.2024.102312
Yang Zhang , Tianming Zha , Guoxin Song , Gulibositan Abudurousuli , Jinxin Che , Fei Zhao , Lin Zhang , Xing Zhang , Bo Gui , Linjia Zhu
{"title":"Unveiling the protective role of sevoflurane in video-assisted thoracoscopic surgery associated-acute lung injury: Inhibition of ferroptosis","authors":"Yang Zhang ,&nbsp;Tianming Zha ,&nbsp;Guoxin Song ,&nbsp;Gulibositan Abudurousuli ,&nbsp;Jinxin Che ,&nbsp;Fei Zhao ,&nbsp;Lin Zhang ,&nbsp;Xing Zhang ,&nbsp;Bo Gui ,&nbsp;Linjia Zhu","doi":"10.1016/j.pupt.2024.102312","DOIUrl":"10.1016/j.pupt.2024.102312","url":null,"abstract":"<div><p>Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe<sup>2+</sup>, glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe<sup>2+</sup> concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102312"},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The involvement of Sting in exacerbating acute lung injury in sepsis via the PARP-1/NLRP3 signaling pathway 蜇伤通过 PARP-1/NLRP3 信号通路参与加重败血症急性肺损伤的过程
IF 3.2 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-06-05 DOI: 10.1016/j.pupt.2024.102303
Tingting Ying , Yulong Yu , Qimin Yu, Gang Zhou, Lingyang Chen, Yixiao Gu, Lijun Zhu, Haifeng Ying, Minjuan Chen
{"title":"The involvement of Sting in exacerbating acute lung injury in sepsis via the PARP-1/NLRP3 signaling pathway","authors":"Tingting Ying ,&nbsp;Yulong Yu ,&nbsp;Qimin Yu,&nbsp;Gang Zhou,&nbsp;Lingyang Chen,&nbsp;Yixiao Gu,&nbsp;Lijun Zhu,&nbsp;Haifeng Ying,&nbsp;Minjuan Chen","doi":"10.1016/j.pupt.2024.102303","DOIUrl":"10.1016/j.pupt.2024.102303","url":null,"abstract":"<div><h3>Background</h3><p>Interferon gene stimulator (Sting) is an indispensable adaptor protein that plays a crucial role in acute lung injury (ALI) induced by sepsis, and the PARP-1/NLRP3 signaling pathway may be an integral component of the inflammatory response mediated by Sting. However, the regulatory role of Sting in the PARP-1/NLRP3 pathway in ALI remains insufficiently elucidated.</p></div><div><h3>Methods</h3><p>Using lipopolysaccharide (LPS) to induce ALI in C57BL/6 mice and HUVEC cells, an <em>in vivo</em> and <em>in vitro</em> model was established. <em>In vivo</em>, Sting agonists and inhibitors were administered, while <em>in vitro</em>, Sting was knocked down using siRNA. ELISA was employed to quantify the levels of IL-1β, IL-6, and TNF-α. TUNEL staining was conducted to assess cellular apoptosis, while co-immunoprecipitation was utilized to investigate the interaction between Sting and NLRP3. Expression levels of Sting, NLRP3, PARP-1, among others, were assessed via Western blotting and RT-qPCR. Lung HE staining and lung wet/dry ratio were evaluated in the <em>in vivo</em> mouse model. To validate the role of the PARP-1/NLRP3 signaling pathway, PARP-1 inhibitors were employed both <em>in vivo</em> and <em>in vitro</em>.</p></div><div><h3>Results</h3><p><em>In vitro</em> experiments revealed that the Sting agonist group exacerbated LPS-induced pulmonary pathological damage, pulmonary edema, inflammatory response (increased levels of IL-6, TNF-α, and IL-1β), and cellular injury, whereas the Sting inhibitor group significantly ameliorated the aforementioned injuries, with further improvement observed in the combination therapy of Sting inhibitor and PARP-1 inhibitor. Western blotting and RT-qPCR results demonstrated significant suppression of ICAM-1, VCAM-1, NLRP3, and PARP-1 expression in the Sting inhibitor group, with this reduction further enhanced in the Sting inhibitor + PARP-1 inhibitor treatment group, exhibiting opposite outcomes to the agonist. Furthermore, <em>in vitro</em> experiments using HUVEC cell lines validated these findings.</p></div><div><h3>Conclusions</h3><p>Our study provides new insights into the roles of Sting and the PARP-1/NLRP3 signaling pathway in inflammatory responses, offering novel targets for the development of therapeutic interventions against inflammatory reactions.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102303"},"PeriodicalIF":3.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Repeated doses of captopril induce airway hyperresponsiveness by modulating the TRPV1 receptor in rats 重复剂量的卡托普利通过调节 TRPV1 受体诱发大鼠气道高反应性。
IF 3.2 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-05-30 DOI: 10.1016/j.pupt.2024.102302
Janiana Raíza Jentsch Matias de Oliveira , Mayara Alves Amorim , Vitor Hélio de Souza Oliveira , Daniela de Almeida Cabrini , Michel Fleith Otuki , Claudia Martins Galindo , Bruna Barbosa da Luz , Maria Fernanda de Paula Werner , João Batista Calixto , Eunice André
{"title":"Repeated doses of captopril induce airway hyperresponsiveness by modulating the TRPV1 receptor in rats","authors":"Janiana Raíza Jentsch Matias de Oliveira ,&nbsp;Mayara Alves Amorim ,&nbsp;Vitor Hélio de Souza Oliveira ,&nbsp;Daniela de Almeida Cabrini ,&nbsp;Michel Fleith Otuki ,&nbsp;Claudia Martins Galindo ,&nbsp;Bruna Barbosa da Luz ,&nbsp;Maria Fernanda de Paula Werner ,&nbsp;João Batista Calixto ,&nbsp;Eunice André","doi":"10.1016/j.pupt.2024.102302","DOIUrl":"10.1016/j.pupt.2024.102302","url":null,"abstract":"<div><p>Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B<sub>2</sub> antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102302"},"PeriodicalIF":3.2,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetic variability of CFTR modulators from standard and alternative regimens 标准方案和替代方案中 CFTR 调节剂的药代动力学变异性。
IF 3.2 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-05-24 DOI: 10.1016/j.pupt.2024.102301
Natalie R. Rose, Ashritha R. Chalamalla, Bryan A. Garcia, Stefanie Krick, Jonathan Bergeron, Hossein Sadeghi, Dennis E. Schellhase, Kevin J. Ryan, Alexander E. Dowell, Edward P. Acosta, Jennifer S. Guimbellot
{"title":"Pharmacokinetic variability of CFTR modulators from standard and alternative regimens","authors":"Natalie R. Rose,&nbsp;Ashritha R. Chalamalla,&nbsp;Bryan A. Garcia,&nbsp;Stefanie Krick,&nbsp;Jonathan Bergeron,&nbsp;Hossein Sadeghi,&nbsp;Dennis E. Schellhase,&nbsp;Kevin J. Ryan,&nbsp;Alexander E. Dowell,&nbsp;Edward P. Acosta,&nbsp;Jennifer S. Guimbellot","doi":"10.1016/j.pupt.2024.102301","DOIUrl":"10.1016/j.pupt.2024.102301","url":null,"abstract":"<div><p>Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102301"},"PeriodicalIF":3.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Shedding light on vitamin D in tuberculosis: A comprehensive review of clinical trials and discrepancies 揭示结核病中的维生素 D:全面回顾临床试验和差异。
IF 3.2 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-05-07 DOI: 10.1016/j.pupt.2024.102300
Alan Santos-Mena , Oscar E. González-Muñiz , Yolanda M. Jacobo-Delgado, Bruno Rivas-Santiago
{"title":"Shedding light on vitamin D in tuberculosis: A comprehensive review of clinical trials and discrepancies","authors":"Alan Santos-Mena ,&nbsp;Oscar E. González-Muñiz ,&nbsp;Yolanda M. Jacobo-Delgado,&nbsp;Bruno Rivas-Santiago","doi":"10.1016/j.pupt.2024.102300","DOIUrl":"10.1016/j.pupt.2024.102300","url":null,"abstract":"<div><p>Over the past few decades, there has been extensive research on the use of vitamin D as an adjunctive therapy in the treatment and prevention of tuberculosis. In vitro studies have provided valuable insights into the mechanisms by which vitamin D activates the immune response to combat <em>Mycobacterium tuberculosis</em>. These encouraging findings have spurred clinical investigations globally to assess the effectiveness of vitamin D as a preventive measure and as an adjunctive treatment for tuberculosis. However, the results from these clinical studies have been contradictory, with some demonstrating clear efficacy while others report only modest or no activity. In this review, we aim to analyze the clinical studies on vitamin D and examine the possible discrepancies observed in their outcomes.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"85 ","pages":"Article 102300"},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant 评估使用低全球升温潜能值推进剂通过加压计量吸入器给药的二丙酸倍氯米松/福莫特罗烟酸酯/溴化甘草酸铵的药代动力学。
IF 3.2 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-04-23 DOI: 10.1016/j.pupt.2024.102299
François Rony , Mauro Cortellini , Alessandro Guasconi , Kusum S. Mathews , Annalisa Piccinno , Gianluigi Poli , Frédéric Vanhoutte , Jelle Klein
{"title":"Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant","authors":"François Rony ,&nbsp;Mauro Cortellini ,&nbsp;Alessandro Guasconi ,&nbsp;Kusum S. Mathews ,&nbsp;Annalisa Piccinno ,&nbsp;Gianluigi Poli ,&nbsp;Frédéric Vanhoutte ,&nbsp;Jelle Klein","doi":"10.1016/j.pupt.2024.102299","DOIUrl":"10.1016/j.pupt.2024.102299","url":null,"abstract":"<div><h3>Introduction</h3><p>Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential.</p><p>The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a.</p></div><div><h3>Methods</h3><p>The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer.</p><p>All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (C<sub>max</sub>) and area under the plasma concentration–time curve between time zero and the last quantifiable timepoint (AUC<sub>0–t</sub>) for the analytes were between 80 and 125 %.</p></div><div><h3>Results</h3><p>In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB C<sub>max</sub> in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for C<sub>max</sub> and 127.34 % for AUC<sub>0–t</sub>). In Study 1, GB AUC<sub>0–t</sub> lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for C<sub>max</sub> and 129.12 % for AUC<sub>0–t</sub>. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC<sub>0–t</sub>, although not for C<sub>max</sub>. Both formulations were similarly well tolerated in all three studies.</p></div><div><h3>Conclusions</h3><p>Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/<span>FF</span>/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"85 ","pages":"Article 102299"},"PeriodicalIF":3.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553924000154/pdfft?md5=574f99472df77217cdeedb51aa0e81c2&pid=1-s2.0-S1094553924000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Suboptimal peak inspiratory flow rate in dry-powder inhaler users for chronic obstructive pulmonary disease in Korea 韩国慢性阻塞性肺病干粉吸入器使用者吸气流速峰值不达标的情况
IF 3.2 3区 医学
Pulmonary pharmacology & therapeutics Pub Date : 2024-04-10 DOI: 10.1016/j.pupt.2024.102298
Ji-Yong Moon , Sang Hyuk Kim , Youlim Kim , Hyun Lee , Chin Kook Rhee , Seung Won Ra , Chang Youl Lee , Joo Hun Park , Yong Bum Park , Kwang Ha Yoo
{"title":"Suboptimal peak inspiratory flow rate in dry-powder inhaler users for chronic obstructive pulmonary disease in Korea","authors":"Ji-Yong Moon ,&nbsp;Sang Hyuk Kim ,&nbsp;Youlim Kim ,&nbsp;Hyun Lee ,&nbsp;Chin Kook Rhee ,&nbsp;Seung Won Ra ,&nbsp;Chang Youl Lee ,&nbsp;Joo Hun Park ,&nbsp;Yong Bum Park ,&nbsp;Kwang Ha Yoo","doi":"10.1016/j.pupt.2024.102298","DOIUrl":"https://doi.org/10.1016/j.pupt.2024.102298","url":null,"abstract":"<div><h3>Background</h3><p>A suboptimal peak inspiratory flow rate (PIFR) in dry-powder inhaler (DPI) users can lead to insufficient therapeutic effects in the treatment of chronic obstructive pulmonary disease (COPD). However, few data on the prevalence of and factors associated with suboptimal PIFR in Korean patients with COPD are available.</p></div><div><h3>Methods</h3><p>We conducted a cross-sectional study of patients with COPD who had been using DPIs for more than three months. PIFR was measured using an In-Check DIAL G16 device. Suboptimal PIFR was defined as below the resistance-matched threshold. Multivariable logistic regression analysis was used to determine factors associated with suboptimal PIFR.</p></div><div><h3>Results</h3><p>Of 444 DPI users with COPD, the rate of suboptimal PIFR was 22.0 % (98/444). In a multivariable analysis, significant factors associated with suboptimal PIFR were age (adjusted odds ratio [aOR] = 1.06 by 1-year increase; 95 % confidence interval [CI] = 1.02–1.09), male sex (aOR = 0.28; 95 % CI = 0.11–0.73), body mass index (BMI) (aOR = 0.91 by 1 kg/m<sup>2</sup> increase; 95 % CI = 0.85–0.99), post-bronchodilator forced vital capacity (FVC) %pred (aOR = 0.97 by 1%pred increase; 95 % CI = 0.95–0.99), and In-Check DIAL R2-type inhaler [medium-low resistance] use (aOR = 3.70 compared with R1-type inhalers [low resistance]; 95 % CI = 2.03–7.03).</p></div><div><h3>Conclusions</h3><p>In Korea, more than one-fifth of DPI users with COPD had a suboptimal PIFR. The factors associated with suboptimal PIFR were age, female gender, low BMI, low FVC, and R2-type inhaler use. Therefore, clinicians should carefully evaluate the possibility of suboptimal PIFR when prescribing DPIs.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"85 ","pages":"Article 102298"},"PeriodicalIF":3.2,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553924000142/pdfft?md5=b93e2894d7969eaf9d3d3e9beac1d9f6&pid=1-s2.0-S1094553924000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140618137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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