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Pulmonary pharmacokinetics

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https://www.readbyqxmd.com/read/28648640/pulmonary-delivery-of-synergistic-combination-of-fluoroquinolone-antibiotic-complemented-with-proteolytic-enzyme-a-novel-antimicrobial-and-antibiofilm-strategy
#1
Purnima V Gupta, Abhijit M Nirwane, Tejashree Bellubi, Mangal S Nagarsenker
Bacterial resistance remains a major hindrance in treatment with antimicrobial agents. Therefore, we assessed the improved antimicrobial and antibiofilm activity of Levofloxacin (LFX) and Serratiopeptidase (SRP) combinations in in vitro microbiological studies. Further, pharmacodynamic and pharmacokinetic studies of liposomal LFX in combination with SRP (LFX liposome-SRP) were performed in S. aureus infected rats. LFX at sub-MIC with SRP eradicated >90% of the preformed biofilm. The entrapment efficiency of LFX in liposome was >80% and the co-spray dried product had MMAD <5μ...
June 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#2
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28639216/biocomparison-study-of-adult-and-paediatric-dose-strengths-of-the-prostacyclin-receptor-agonist-selexipag
#3
Margaux Boehler, Shirin Bruderer, Ivan Ulč, Jasper Dingemanse
BACKGROUND AND OBJECTIVES: Selexipag is an oral, non-prostanoid, selective prostacyclin receptor agonist recently marketed for the treatment of pulmonary arterial hypertension (PAH) in adults. Selexipag may also be an effective treatment in children with PAH. The aim of this study was to compare the pharmacokinetics of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) vs. 4 paediatric tablets of 50 µg (Treatment B) in healthy adult male subjects...
June 21, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28615638/pharmacodynamic-and-pharmacokinetic-assessment-of-pulmonary-rehabilitation-mixture-for-the-treatment-of-pulmonary-fibrosis
#4
Juanjuan Zhao, Yan Ren, Yubei Qu, Wanglin Jiang, Changjun Lv
Pulmonary rehabilitation mixture (PRM), a Chinese herbal medicine formula, has been used to treat pulmonary fibrosis for decades. In this study, we systematically evaluated the pharmacodynamic and pharmacokinetic performance of PRM. The pharmacodynamic results showed that PRM could improve the condition of CoCl2-stimulated human type II alveolar epithelial cells, human pulmonary microvascular endothelial cells, human lung fibroblasts and pulmonary fibrosis rats induced by bleomycin, PRM treatment reduced the expression of platelet-derived growth factor, fibroblast growth factor, toll-like receptor 4, high-mobility group box protein 1 and hypoxia-inducible factor 1α...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611243/optimization-of-a-collagen-targeted-positron-emission-tomography-probe-for-molecular-imaging-of-pulmonary-fibrosis
#5
Pauline Désogère, Luis F Tapias, Tyson A Rietz, Nicholas Rotile, Francesco Blasi, Helen Day, Justin Elliot, Bryan C Fuchs, Michael Lanuti, Peter Caravan
There is a large unmet need for a simple, accurate, non-invasive, quantitative and high resolution imaging modality to detect lung fibrosis at early stage and to monitor disease progression. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe the optimization of a collagen-targeted positron emission tomography (PET) probe for staging pulmonary fibrosis. Methods: Six peptides were synthesized, conjugated to a copper chelator, and radiolabeled with copper-64. The collagen affinity of each probe was measured in a plate-based assay...
June 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28597762/the-safety-and-pharmacokinetics-of-rapid-iloprost-aerosol-delivery-via-the-breelib-nebulizer-in-pulmonary-arterial-hypertension
#6
Tobias Gessler, Hossein-Ardeschir Ghofrani, Matthias Held, Hans Klose, Hanno Leuchte, Horst Olschewski, Stephan Rosenkranz, Lueder Fels, Na Li, Dawn Ren, Andreas Kaiser, Marcus-Hillert Schultze-Mosgau, Bernhard Müllinger, Beate Rohde, Werner Seeger
The BREELIB nebulizer was developed for iloprost to reduce inhalation times for patients with pulmonary arterial hypertension (PAH). This multicenter, randomized, unblinded, four-part study compared inhalation time, pharmacokinetics, and acute tolerability of iloprost 5 µg at mouthpiece delivered via BREELIB versus the standard I-Neb nebulizer in 27 patients with PAH. The primary safety outcome was the proportion of patients with a maximum increase in heart rate (HR) ≥ 25% and/or a maximum decrease in systolic blood pressure ≥ 20% within 30 min after inhalation...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28593681/initial-anticoagulation-in-patients-with-pulmonary-embolism-thrombolysis-unfractionated-heparin-lmwh-fondaparinux-or-doacs
#7
REVIEW
Jenneke Leentjens, Mike Peters, Anne C Esselink, Yvo Smulders, Cornelis Kramers
The initial treatment of hemodynamically stable patients with pulmonary embolism (PE) has dramatically changed since the introduction of low molecular weight heparins (LMWHs). With the recent discovery of the direct oral anticoagulant drugs (DOACs), initial treatment of PE will be simplified even further. In several large clinical trials it has been demonstrated that DOACs are non-inferior to standard therapy for the initial treatment of PE, and because of their practicability they are becoming the agents of first choice...
June 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28584996/endpoint-assessment-in-rabbit-models-of-invasive-pulmonary-aspergillosis-and-mucormycosis
#8
Vidmantas Petraitis, Ruta Petraitiene, William W Hope, Thomas J Walsh
Multiple animal models have been developed to study the pathogenesis of invasive pulmonary aspergillosis, as well as to evaluate the efficacy, pharmacokinetics, and pharmacodynamics of various antifungal agents and vaccines. Each model is beneficial depending on the questions that are asked. In this chapter, we will discuss the endpoints assessment of the persistently neutropenic rabbit models of invasive pulmonary aspergillosis and invasive pulmonary mucormycosis.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28577680/results-of-a-phase-i-ii-multi-center-investigation-of-udenafil-in-adolescents-after-fontan-palliation
#9
David J Goldberg, Victor Zak, Bryan H Goldstein, Shan Chen, Michelle S Hamstra, Elizabeth A Radojewski, Eileen Maunsell, Seema Mital, Shaji C Menon, Kurt R Schumacher, R Mark Payne, Mario Stylianou, Jonathan R Kaltman, Tina M deVries, James L Yeager, Stephen M Paridon
BACKGROUND: The Fontan operation results in a circulation that is dependent on low pulmonary vascular resistance to maintain an adequate cardiac output. Medical therapies that lower pulmonary vascular resistance may augment cardiac output and improve long-term outcomes. OBJECTIVES: This phase I/II clinical trial conducted by the Pediatric Heart Network was designed to evaluate short-term safety, pharmacokinetics (PK), and preliminary efficacy of udenafil in adolescents following Fontan...
June 2017: American Heart Journal
https://www.readbyqxmd.com/read/28575278/pharmacokinetics-of-nebulized-colistin-methanesulfonate-in-critically-ill-patients
#10
Matthieu Boisson, Nicolas Grégoire, Marielle Cormier, Patrice Gobin, Sandrine Marchand, William Couet, Olivier Mimoz
Objectives: Optimal dosing for nebulized colistin methanesulfonate (CMS), the prodrug of colistin, is unknown. We describe the pulmonary and systemic pharmacokinetics of CMS and colistin following nebulization of 0.5 million IU (MIU) of CMS in ventilated patients. Methods: Twelve critically ill patients received 0.5 MIU of CMS administered every 8 h as 30 min nebulizations. Blood samples were collected immediately before and until 8 h after first nebulization; mini-bronchoalveolar lavage (mini-BAL) was performed at 1 and 5 h or 3 and 8 h (six patients each) post-dose...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28568482/diffusion-limited-pbpk-model-for-predicting-pulmonary-pharmacokinetics-of-florfenicol-in-pig
#11
M R Qian, Q Y Wang, H Yang, G Z Sun, X B Ke, L L Huang, J D Gao, J J Yang, B Yang
For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion-limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion-limited lung, flow-limited muscle, liver, and kidney and an extra compartment representing the remaining carcass...
June 1, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28559256/aerosolized-polymyxin-b-for-treatment-of-respiratory-tract-infections-determination-of-pharmacokinetic-pharmacodynamic-indices-for-aerosolized-polymyxin-b-against-pseudomonas-aeruginosa-in-a-mouse-lung-infection-model
#12
Yu-Wei Lin, Qi Tony Zhou, Nikolas J Onufrak, Veronika Wirth, Ke Chen, Jiping Wang, Alan Forrest, Hak-Kim Chan, Jian Li
Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD) and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were conducted in neutropenic infected mice and the data were analyzed by a population PK model...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28558828/eprinomectin-pour-on-eprinex%C3%A2-pour-on-merial-efficacy-against-gastrointestinal-and-pulmonary-nematodes-and-pharmacokinetics-in-sheep
#13
Dietmar Hamel, Antonio Bosco, Laura Rinaldi, Giuseppe Cringoli, Karl-Heinz Kaulfuß, Michael Kellermann, James Fischer, Hailun Wang, Katrin Kley, Sandra Mayr, Renate Rauh, Martin Visser, Thea Wiefel, Becky Fankhauser, Steffen Rehbein
BACKGROUND: The anthelmintic efficacy of the 0.5% w/v topical formulation of eprinomectin (EPN), EPRINEX® Pour-on (Merial) when administered at 1 mg/kg body weight was evaluated in sheep in two dose confirmation laboratory studies and one multicenter field study. In addition, the pharmacokinetics of EPN when administered at that dosage to adult sheep was determined. RESULTS: In the two dose confirmation studies, which included 10 sheep each, sheep treated with topical EPN had significantly (p < 0...
May 30, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28556581/population-modeling-of-selexipag-pharmacokinetics-and-clinical-response-parameters-in-patients-with-pulmonary-arterial-hypertension
#14
A Krause, M Machacek, D Lott, N Hurst, S Bruderer, J Dingemanse
Selexipag (Uptravi) is an oral selective IP prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal GRIPHON study was the largest clinical study ever conducted in PAH patients, providing long-term data from 1,156 patients. PAH comedication did not affect exposure to selexipag, while exposure to its active metabolite ACT-333679 was reduced by 30% when taken in combination, clinically not relevant in the context of individual dose up-titration. Using log-linear regression models linking model-predicted steady-state exposure to pharmacodynamics (PD), exposure to selexipag and ACT-333679 showed some statistically significant, albeit not clinically relevant, effects on exercise capacity, laboratory values, and the occurrence of prostacyclin-related adverse events, but not on vital signs or adverse events denoting hemorrhage...
May 27, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28533253/selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#15
Zachary R Noel, Kazuhiko Kido, Tracy E Macaulay
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosing and administration, and place in therapy of selexipag, an orally administered selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH), are reviewed. SUMMARY: The first-in-class oral prostacyclin IP receptor agonist selexipag (Uptravi, Actelion Pharmaceuticals) was approved by the Food and Drug Administration in December 2015...
May 22, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28528008/-role-of-therapeutic-drug-monitoring-in-pulmonary-infections
#16
REVIEW
C Padoin
Pulmonary infections are common and caused by a wide range of viruses, bacteria, parasites and fungi. They consist of lower respiratory tract infections with community and hospital acquired acute pneumonia, bronchitis, lung abscess, fungal infections and tuberculosis. The management of these infections should be based on guidelines that take into account the microorganisms most frequently involved as a basis for empirical treatment, with identification of causative microorganisms allowing targeted treatments...
May 17, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28524738/selexipag-a-selective-prostacyclin-receptor-agonist-in-pulmonary-arterial-hypertension-a-pharmacology-review
#17
Jesús Honorato Pérez
Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways. Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag...
July 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28523172/roles-of-roflumilast-a-selective-phosphodiesterase-4-inhibitor-in-airway-diseases
#18
REVIEW
Theerasuk Kawamatawong
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases. Both diseases have incompletely distinct pathophysiology, clinical manifestation, and treatment responsiveness. Pulmonary and systemic inflammations are the hallmarks of COPD. Most asthma responds to inhaled corticosteroid (ICS) treatment. In contrast, COPD is a corticosteroid-resistant disease. Bronchodilators are a preferred treatment method of COPD, with the aim of improving symptoms and preventing exacerbation...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28518128/an-in-vitro-caseum-binding-assay-that-predicts-drug-penetration-in-tuberculosis-lesions
#19
Jansy P Sarathy, Hsin-Pin Ho Liang, Danielle Weiner, Jacqueline Gonzales, Laura E Via, Véronique Dartois
The eradication of tuberculosis disease requires drug regimens that can penetrate the multiple layers of complex pulmonary lesions. Drug distribution in the caseous cores of cavities and lesions is especially crucial because they harbor subpopulations of drug-tolerant bacteria also commonly referred to as persisters. Existing methods for the measurement of drug penetration in tuberculosis lesions involve costly and time-consuming in vivo pharmacokinetic studies coupled to bioanalytical or imaging techniques...
May 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28510480/dry-powder-inhaler-formulation-of-rifampicin-an-improved-targeted-delivery-system-for-alveolar-tuberculosis
#20
Tejal Rawal, Laurent Kremer, Iman Halloum, Shital Butani
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 dry powder inhaler formulation was prepared by simply mixing micronized rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug were prepared with various lactose grades (Inhalac(®), Respitose,(®) and Lactohale(®))...
May 16, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
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