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Pulmonary pharmacokinetics

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https://www.readbyqxmd.com/read/27904506/safety-and-efficacy-of-tenecteplase-versus-alteplase-in-acute-coronary-syndrome-a-systematic-review-and-meta-analysis-of-randomized-trials
#1
REVIEW
Alexandre Guillermin, David Jun Yan, Arnaud Perrier, Christophe Marti
INTRODUCTION: Alteplase and tenecteplase are two widely used thrombolytic agents and are both approved for the treatment of acute myocardial infarction. These two molecules have increased fibrin specificity compared with older thrombolytics but distinct pharmacokinetic properties and may differ in terms of risks and benefits. We decided to review the available evidence comparing the safety and efficacy of these two molecules in acute coronary syndrome (ACS) or pulmonary embolism (PE)...
December 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27889253/blood-and-tissue-distribution-of-posaconazole-in-a-rat-model-of-invasive-pulmonary-aspergillosis
#2
E Cendejas-Bueno, A Forastiero, I Ruiz, E Mellado, J Gavaldà, A Gomez-Lopez
Posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. The objective of this study is to obtain pharmacokinetic (PK) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. The PK parameters in lung samples were systematically higher than in serum. After multiple-dose administration of posaconazole, a significant accumulation of the drug was evident in lung tissue...
October 11, 2016: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/27872700/pharmacokinetic-study-of-furosemide-incorporated-plga-microspheres-after-oral-administration-to-rat
#3
Katayoun Derakhshandeh, Moin Karimi, Abbas Hemati Azandaryani, Gholamreza Bahrami, Kiumras Ghanbari
OBJECTIVES: The purpose of the current study was to assess the feasibility of microspheres from biocompatible polymer for oral bioavailability (BA) enhancement of potent sulfonamide- type loop diuretic- Furosemide - which used in the treatment of congestive heart failure, caused edema, cirrhosis, renal disease and as an adjunct in acute pulmonary edema. The comparatively poor and inconstant BA of furosemide, which occurs site-specifically in the stomach and upper small intestine, has been ascribed to the poor dissolution of furosemide...
October 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27869892/-anmco-position-paper-use-of-new-oral-anticoagulants-for-the-treatment-and-prevention-of-pulmonary-thromboembolism
#4
Iolanda Enea, Loris Roncon, Michele Massimo Gulizia, Michele Azzarito, Cecilia Becattini, Amedeo Bongarzoni, Franco Casazza, Claudio Cuccia, Carlo D'Agostino, Matteo Rugolotto, Marco Vatrano, Eugenio Vinci, Paride Fenaroli, Dario Formigli, Paolo Silvestri, Federico Nardi, Maria Cristina Vedovati, Marino Scherillo
The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including 1) their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in the acute phase with the "double drug single dose" approach or with "single drug double dose"; 3) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; 4) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance >30 ml/min), the elderly (>75 years); 5) they propose a possible laboratory clinical pathway for follow-up; 6) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications...
September 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/27863483/estimation-of-tulathromycin-depletion-in-plasma-and-milk-after-subcutaneous-injection-in-lactating-goats-using-a-nonlinear-mixed-effects-pharmacokinetic-modeling-approach
#5
Zhoumeng Lin, Matthew Cuneo, Joan D Rowe, Mengjie Li, Lisa A Tell, Shayna Allison, Jan Carlson, Jim E Riviere, Ronette Gehring
BACKGROUND: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i...
November 18, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27842973/pharmacokinetics-of-ethionamide-delivered-in-spray-dried-microparticles-to-the-lungs-of-guinea-pigs
#6
Lucila Garcia-Contreras, Danielle J Padilla-Carlin, Jean Sung, Jarod VerBerkmoes, Pavan Muttil, Katharina Elbert, Charles Peloquin, David Edwards, Anthony Hickey
The use of ethionamide (ETH) in treating multidrug-resistant tuberculosis is limited by severe side effects. ETH disposition after pulmonary administration in spray-dried particles might minimize systemic exposure and side effects. To explore this hypothesis, spray-dried ETH particles were optimized for performance in a dry powder aerosol generator and exposure chamber. ETH particles were administered by the intravenous (IV), oral, or pulmonary routes to guinea pigs. ETH appearance in plasma, bronchoalveolar lavage, and lung tissues was measured and subjected to noncompartmental pharmacokinetic analysis...
November 11, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27832142/predictors-of-prolonged-tb-treatment-in-a-dutch-outpatient-setting
#7
Natasha Van't Boveneind-Vrubleuskaya, Alper Daskapan, Jos G W Kosterink, Tjip S van der Werf, Susan van den Hof, Jan-Willem C Alffenaar
INTRODUCTION: Standard treatment duration for drug-susceptible tuberculosis (TB) treatment is 6 months. Treatment duration is often extended-and for various different reasons. The aim of this study was to determine the prevalence and to assess risk factors associated with extended TB treatment. METHODS: A cross-sectional study was conducted. Data including demographic, clinical, radiological and microbiological information from the Netherlands TB Register (NTR) of 90 patients with smear and culture positive pulmonary TB of the region Haaglanden, The Netherlands, was eligible for analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27821710/exploration-of-%C3%AE-1-antitrypsin-treatment-protocol-for-islet-transplantation-dosing-plan-and-route-of-administration
#8
Boris M Baranovski, Eyal Ozeri, Galit Shahaf, David E Ochayon, Ronen Schuster, Nofar Bahar, Noa Kalay, Pablo Cal, Mark I Mizrahi, Omer Nisim, Pnina Strauss, Eran Schenker, Eli C Lewis
Life-long weekly infusions of human α1-antitrypsin (hAAT) are currently administered as augmentation therapy for patients with genetic AAT deficiency (AATD). Several recent clinical trials attempt to extend hAAT therapy to conditions outside AATD, including type 1 diabetes. Since the endpoint for AATD is primarily the reduction of risk for pulmonary emphysema, the present study explores hAAT dose protocols and routes of administration in attempt to optimize hAAT therapy for islet-related injury. Islet-grafted mice were treated with hAAT (Glassia™; i...
November 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27821445/substantial-targeting-advantage-achieved-by-pulmonary-administration-of-colistin-methanesulfonate-insights-from-a-large-animal-model
#9
Cornelia B Landersdorfer, Tri-Hung Nguyen, Linh Thuy Lieu, Gary Nguyen, Robert J Bischof, Els N Meeusen, Jian Li, Roger L Nation, Michelle P McIntosh
Colistin, administered as its inactive prodrug colistin methanesulfonate (CMS), is often used in multidrug-resistant Gram-negative pulmonary infections. The CMS and colistin pharmacokinetics in plasma and epithelial lining fluid (ELF) following intravenous and pulmonary dosing have not been evaluated in a large animal model with similar pulmonary architecture to humans.Six merino sheep (34-43kg) received an intravenous or pulmonary dose of 4-8 mg/kg CMS (sodium) or 2-3 mg/kg colistin (sulfate) in a 4-way crossover study...
November 7, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27809616/betrixaban-the-next-direct-factor-xa-inhibitor
#10
Martin Thoenes, Joan Minguet, Karin Bramlage, Peter Bramlage, Carmen Ferrero
Venous thromboembolism is a major global health burden. Since the 1930s, prevention of stroke and pulmonary embolism in these patients has been achieved using conventional anticoagulants, such as heparin and warfarin. However, in recent years, four direct non-vitamin K antagonist oral anticoagulants (DOACs) have entered the market as alternative treatment options. Betrixaban is a fifth DOAC looking to gain marketing approval in the near future, and may have several potentially beneficial properties. Areas covered: Here, we outline the metabolism, pharmacokinetics, and pharmacodynamics of betrixaban, and summarise its clinical efficacy and safety based on the results of phase II/III trials...
December 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27795624/rifampicin-and-anti-hypertensive-drugs-in-chronic-kidney-disease-pharmacokinetic-interactions-and-their-clinical-impact
#11
A Agrawal, S K Agarwal, T Kaleekal, Y K Gupta
Patients on dialysis have an increased incidence of tuberculosis (TB). Rifampicin, a first-line antitubercular therapy (ATT) drug, is a potent inducer of hepatic cytochrome P450 (CYP). There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation...
September 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27776446/inhaled-phage-therapy-a-promising-and-challenging-approach-to-treat-bacterial-respiratory-infections
#12
Elsa Bodier-Montagutelli, Eric Morello, Guillaume l'Hostis, Antoine Guillon, Emilie Dalloneau, Renaud Respaud, Nikita Pallaoro, Hélène Blois, Laurent Vecellio, Jérôme Gabard, Nathalie Heuzé-Vourc'h
Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context...
October 25, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27771434/therapeutic-applications-of-dichloroacetate-and-the-role-of-glutathione-transferase-zeta-1
#13
REVIEW
Margaret O James, Stephan C Jahn, Guo Zhong, Marci G Smeltz, Zhiwei Hu, Peter W Stacpoole
Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen...
October 19, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27762146/combined-qsar-based-virtual-screening-and-fluorescence-binding-assay-to-identify-natural-product-mediators-of-interferon-regulatory-factor-7-irf-7-in-pulmonary-infection
#14
Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/27756196/pharmacokinetic-drug-evaluation-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#15
Mayank Sardana, Matthew Moll, Harrison W Farber
Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy...
December 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27750459/riociguat-for-the-treatment-of-pulmonary-hypertension-a-safety-evaluation
#16
Christina Binder, Caroline Zotter-Tufaro, Diana Bonderman
The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH)...
November 9, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27743211/evaluation-of-a-flexible-nota-rgd-kit-solution-using-gallium-68-from-different-68-ge-68-ga-generators-pharmacokinetics-and-biodistribution-in-nonhuman-primates-and-demonstration-of-solitary-pulmonary-nodule-imaging-in-humans
#17
Thomas Ebenhan, Isabel Schoeman, Daniel D Rossouw, Anne Grobler, Biljana Marjanovic-Painter, Judith Wagener, Hendrik G Kruger, Mike M Sathekge, Jan Rijn Zeevaart
PURPOSE: Radiopharmaceuticals containing the motive tripeptide arginyl-glycyl-asparatic acid (RGD) are known to target ανβ3 integrins during tumor angiogenesis. A more generic kit radiolabeling procedure accommodating Ga-68 from different generators was developed for NOTA-RGD and evaluated for its versatile use and safety in subsequent in vivo applications. The [(68)Ga]NOTA-RGD kit was further verified for its expected biodistribution and pharmacokinetics in nonhuman primates and its clinical sensitivity to detect solitary pulmonary nodules (SPN) in cancer patients...
October 14, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27742208/pharmacodynamic-and-pharmacokinetic-profiling-of-delafloxacin-in-a-murine-lung-model-against-community-acquired-respiratory-tract-pathogens
#18
Abrar K Thabit, Jared L Crandon, David P Nicolau
Increasing antimicrobial resistance in community-acquired pneumonia (CAP) pathogens has contributed to infection-related morbidity and mortality. Delafloxacin is a novel fluoroquinolone with broad-spectrum activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to define the pharmacodynamic profile of delafloxacin against CAP pathogens using a neutropenic murine lung infection model. Five S. pneumoniae, 2 methicillin-susceptible S...
September 29, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27740878/predicting-exposure-after-oral-inhalation-of-the-selective-glucocorticoid-receptor-modulator-azd5423-based-on-dose-deposition-pattern-and-mechanistic-modeling-of-pulmonary-disposition
#19
Per Bäckman, Ulrika Tehler, Bo Olsson
BACKGROUND: Exposure following oral inhalation depends on the deposition pattern of the inhaled aerosol, the extent and rate of oral and pulmonary absorption, as well as systemic distribution and clearance. For lipophilic inhaled compounds with low water solubility and high permeability, the extent and rate of pulmonary absorption can be assumed dependent on deposition pattern as well as dissolution rate. MATERIALS AND METHODS: A mechanistic model of airway deposition, mucociliary clearance, dissolution, absorption, and dissipation was applied to simulate systemic exposure of the novel selective glucocorticoid receptor modulator, AZD5423, when dosed to healthy volunteers using two different nebulizers and two different dry powder inhalers in combination with two different primary particle size distributions...
October 14, 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/27727514/serelaxin-in-acute-heart-failure-most-recent-update-on-clinical-and-preclinical-evidence
#20
Raktim Kumar Ghosh, Kinjal Banerjee, Ramyashree Tummala, Somedeb Ball, Keyvan Ravakhah, Anjan Gupta
Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising health care costs and one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy but eventually found to have a number of other physiological actions, not only in pregnancy, but also in non-pregnant women and men...
October 11, 2016: Cardiovascular Therapeutics
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