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Pulmonary pharmacokinetics

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https://www.readbyqxmd.com/read/28528008/-role-of-therapeutic-drug-monitoring-in-pulmonary-infections
#1
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
#2
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...
May 19, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28523172/roles-of-roflumilast-a-selective-phosphodiesterase-4-inhibitor-in-airway-diseases
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28507469/lungs-deposition-and-pharmacokinetic-study-of-submicron-budesonide-particles-in-wistar-rats-intended-for-immediate-effect-in-asthma
#6
Abdul Rauf, Aseem Bhatnagar, S S Sisodia, Roop K Khar, Farhan J Ahmad
The purpose of the present investigation was to study the aerosolization, lungs deposition and pharmacokinetic study of inhalable submicron particles of budesonide in male Wistar rats. Submicron particles were prepared by antisolvent nanoprecipitation method and freeze-dried to obtain free flowing powder. The freeze-drying process yielded dry powder with desirable aerodynamic properties for inhalation therapy. An in-house model inhaler was designed to deliver medicine to lungs, optimized at dose level of 10 mg for 30 sec of fluidization...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28507117/pharmacokinetics-of-levofloxacin-in-multidrug-and-extensively-drug-resistant-tuberculosis-patients
#7
Natasha Van't Boveneind-Vrubleuskaya, Tatiana Seuruk, Kai van Hateren, Tridia van der Laan, Jos G W Kosterink, Tjip S van der Werf, Dick van Soolingen, Susan van den Hof, Alena Skrahina, Jan-Willem C Alffenaar
Pharmacodynamics are important in treatment of especially multidrug- and extensively resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to minimal inhibitory concentration (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter to predict the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of treatment regimen at a dose of 15 mg/kg once daily...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28494686/clinical-pharmacology-efficacy-and-safety-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#8
Shirin Bruderer, Noémie Hurst, Tatiana Remenova, Jasper Dingemanse
Introduction Selexipag is the first oral, non-prostanoid, selective prostacyclin receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients. Areas covered: This article reviews the clinical pharmacology, efficacy, and safety of selexipag in the treatment of PAH. Expert opinion: Selexipag is the first oral drug that selectively targets the prostacyclin pathway, and has evidence of long-term efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH patients, selexipag significantly reduced the risk of the primary composite outcome of morbidity/mortality (M/M)...
May 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28494463/plasma-drug-concentrations-in-patients-with-pulmonary-arterial-hypertension-on-combination-treatment
#9
Ekkehard Grünig, Johanna Ohnesorge, Nicola Benjamin, Jürgen Burhenne, Yeliz Enderle, Benjamin Egenlauf, Christine Fischer, Satenik Harutyunova, Andrea Huppertz, Hans Klose, Walter E Haefeli
BACKGROUND: Combination therapy with the phosphodiesterase type 5 inhibitors (PDE-5i) sildenafil or tadalafil and the endothelin receptor antagonists (ERA) bosentan, ambrisentan, or macitentan may cause mutual pharmacokinetic interactions in patients with pulmonary arterial hypertension (PAH). OBJECTIVE: The objective of this study was to analyze plasma drug concentrations in PAH patients receiving different combination treatments. METHODS: PAH patients receiving a stable combination treatment with ERA and PDE-5i with targeted dosage for at least 1 month were routinely assessed, including clinical parameters and plasma drug concentrations...
May 12, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28491268/umeclidinium-in-chronic-obstructive-pulmonary-disease-latest-evidence-and-place-in-therapy
#10
REVIEW
Kesavan Suresh Babu, Jaymin Bhagwanji Morjaria
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and health care expenditure throughout the world. COPD guidelines recommend the use of long-acting muscarinic antagonist (LAMA) either alone or in combination with a long-acting β2 agonist (LABA). For over 10 years, tiotropium was the only LAMA that was used in the management of COPD. Over the past few years, various new drugs have been identified that act on the muscarinic receptors and β2 receptors. Umeclidinium (Umec) is a new LAMA currently approved for use in patients with COPD either as monotherapy or in combination with vilanterol (Vil)...
April 2017: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/28482017/evaluation-of-nicotine-pharmacokinetics-and-subjective-effects-following-use-of-a-novel-nicotine-delivery-system
#11
Axel Teichert, Patrick Brossard, Loyse Felber Medlin, Larissa Sandalic, Mikael Franzon, Chris Wynne, Murray Laugesen, Frank Lüdicke
Introduction: Novel nicotine delivery systems represent an evolving part of the tobacco harm reduction strategy. The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette® inhalator were evaluated. Methods: This open-label, ascending nicotine levels study was conducted in 16 healthy smokers. Three different nicotine delivery levels, 50, 80, and 150 µg/puff delivered by the P3L system were evaluated consecutively on different days, after the use of the Nicorette® inhalator...
May 6, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28471727/safety-and-clinical-activity-of-the-programmed-death-ligand-1-inhibitor-durvalumab-in-combination-with-poly-adp-ribose-polymerase-inhibitor-olaparib-or-vascular-endothelial-growth-factor-receptor-1-3-inhibitor-cediranib-in-women-s-cancers-a-dose-escalation
#12
Jung-Min Lee, Ashley Cimino-Mathews, Cody J Peer, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Liang Cao, Maria I Harrell, Elizabeth M Swisher, Nicole Houston, Dana-Adriana Botesteanu, Janis M Taube, Elizabeth Thompson, Aleksandra Ogurtsova, Haiying Xu, Jeffers Nguyen, Tony W Ho, William D Figg, Elise C Kohn
Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling by vascular endothelial growth factor receptor inhibition may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients and Methods This phase I study tested durvalumab doublets in parallel 3 + 3 dose escalations...
May 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28469033/a-highly-potent-extended-half-life-antibody-as-a-potential-rsv-vaccine-surrogate-for-all-infants
#13
Qing Zhu, Jason S McLellan, Nicole L Kallewaard, Nancy D Ulbrandt, Susan Palaszynski, Jing Zhang, Brian Moldt, Anis Khan, Catherine Svabek, Josephine M McAuliffe, Daniel Wrapp, Nita K Patel, Kimberly E Cook, Bettina W M Richter, Patricia C Ryan, Andy Q Yuan, JoAnn A Suzich
Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose...
May 3, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28467730/combination-therapy-for-the-treatment-of-pulmonary-mold-infections
#14
Matthew William McCarthy, Vidmantas Petraitis, Thomas J Walsh
Pulmonary mold infections are caused by ubiquitous organisms found in soil, water, and decaying vegetation, including Aspergillus spp., the Mucormycetes, hyaline molds, and dematiaceous (black) molds. Areas covered: These infections are often a challenge to diagnose and even more difficult to treat. Recently, antifungal combination therapy has emerged as a promising strategy to treat some forms of invasive mycoses, including pulmonary mold infections. Historically, this approach has been limited due to non-uniform interpretation criteria, variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination, and an inability to predict clinical success based on in vitro data and animal models...
May 9, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28461315/genetic-determinants-of-the-pharmacokinetic-variability-of-rifampicin-in-malawian-adults-with-pulmonary-tuberculosis
#15
Derek J Sloan, Andrew D McCallum, Alessandro Schipani, Deirdre Egan, Henry C Mwandumba, Steve A Ward, David Waterhouse, Gertrude Banda, Theresa J Allain, Andrew Owen, Saye H Khoo, Geraint R Davies
Variable exposure to anti-tuberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampicin. We evaluated the contribution of Single Nucleotide Polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC, CES-1) to inter-individual pharmacokinetic variability in Malawi. 174 adults with pulmonary TB underwent sampling of plasma rifampicin concentrations at 2- and 6-hours post-dose...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28461311/population-pharmacokinetic-modeling-as-a-tool-to-characterize-the-decrease-in-ciprofloxacin-free-interstitial-levels-caused-by-pseudomonas-aeruginosa-biofilm-lung-infection-in-wistar-rats
#16
Bruna G S Torres, Victória E Helfer, Priscila M Bernardes, Alexandre José Macedo, Elisabet I Nielsen, Lena E Friberg, Teresa Dalla Costa
Biofilm formation plays an important role in the persistence of pulmonary infections, for example in cystic fibrosis patients. So far, little is known about antimicrobials lung disposition in biofilm-associated pneumonia. This study aimed to evaluate, by microdialysis, ciprofloxacin (CIP) penetration into the lungs of healthy and Pseudomonas aeruginosa biofilm infected rats and to develop a comprehensive model to describe the CIP disposition in both conditions. P. aeruginosa was immobilized into alginate beads and intratracheally inoculated 14 days before CIP administration (20 mg/kg)...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28457009/comparison-of-direct-sampling-and-brochoalveolar-lavage-for-determining-active-drug-concentrations-in-the-pulmonary-epithelial-lining-fluid-of-calves-injected-with-enrofloxacin-or-tilmicosin
#17
D M Foster, H J Sylvester, M G Papich
Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril(®) 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil(®) 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC...
April 29, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28431781/clenbuterol-hydrochloride
#18
Abdulrahman A Al-Majed, Nasr Y Khalil, Ibraheem Khbrani, Hatem A Abdel-Aziz
Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28416418/current-progress-toward-a-better-understanding-of-drug-disposition-within-the-lungs-summary-proceedings-of-the-1-st-workshop-on-drug-transporters-in-the-lungs
#19
REVIEW
Carsten Ehrhardt, Per Bäckman, William Couet, Chris Edwards, Ben Forbes, Markus Fridén, Mark Gumbleton, Ken-Ichi Hosoya, Yukio Kato, Takeo Nakanishi, Mikihisa Takano, Tetsuya Terasaki, Ryoko Yumoto
The School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin hosted the 1(st)Workshop on Drug Transporters in the Lungs in September 2016 to discuss the impact of transporters on pulmonary drug disposition and their roles as drug targets in lung disease. The workshop brought together about 30 scientists from academia and pharmaceutical industry from Europe and Japan and addressed the primary questions: What do we know today, and what do we need to know tomorrow about transporters in the lung? The three themes of the workshop were: (1) techniques to study drug transporter expression and actions in the lungs; (2) drug transporter effects on pulmonary pharmacokinetics - case studies; and (3) transporters as drug targets in lung disease...
April 14, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28415455/heparin-modified-graphene-oxide-for-ph-sensitive-sustained-release-of-doxorubicin-hydrochloride
#20
Baomei Zhang, Xiaoye Yang, Yang Wang, Guangxi Zhai
A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
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