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Pulmonary pharmacokinetics

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https://www.readbyqxmd.com/read/29341619/a-new-folate-grafted-chitosan-derivative-to-improve-the-delivery-of-paclitaxel-loaded-solid-lipid-nanoparticles-for-lung-tumour-therapy-by-inhalation
#1
Remi Rosiere, Matthias Van Woensel, Michel Gelbcke, Véronique Mathieu, Julien Hecq, Thomas Mathivet, Marjorie Vermeersch, Pierre G Van Antwerpen, Karim Amighi, Nathalie Wauthoz
Inhaled chemotherapy for the treatment of lung tumours requires that drug delivery systems improve selectivity for cancer cells and tumour penetration and allow sufficient lung residence. To this end, we developed solid lipid nanoparticles (SLN) with modified surface properties. We successfully synthesized a new folate-grafted copolymer of polyethylene glycol (PEG) and chitosan, F-PEG-HTCC, with a PEG-graft ratio of 7% and a molecular weight range of 211-250 kDa. F-PEG-HTCC-coated, paclitaxel-loaded SLN were prepared with an encapsulation efficiency, mean diameter and zeta potential of about 100%, 250 nm and +32 mV, respectively...
January 17, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29334814/dual-ligand-modified-liposomes-provide-effective-local-targeted-delivery-of-lung-cancer-drug-by-antibody-and-tumor-lineage-homing-cell-penetrating-peptide
#2
Congcong Lin, Xue Zhang, Hubiao Chen, Zhaoxiang Bian, Ge Zhang, Muhammad Kashif Riaz, Deependra Tyagi, Ge Lin, Yanbo Zhang, Jinjin Wang, Aiping Lu, Zhijun Yang
The abilities of a drug delivery system to target and penetrate tumor masses are key factors in determining the system's chemotherapeutic efficacy. Here, we explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to simultaneously enhance the tumor-specific targeting and increase tumor cell penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in CA IX-positive lung cancer cells, which showed tunable size (137...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29327219/pharmacological-insights-into-the-use-of-apomorphine-in-parkinson-s-disease-clinical-relevance
#3
REVIEW
Manon Auffret, Sophie Drapier, Marc Vérin
The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson's disease (PD). The chemistry, structure-activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic...
January 11, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29313863/pharmacokinetics-of-high-dose-extended-infusion-meropenem-during-pulmonary-exacerbation-in-adult-cystic-fibrosis-patients-a-case-series
#4
Emanuele Delfino, Carmen Fucile, Valerio Del Bono, Anna Marchese, Valeria Marini, Erika Coppo, Rosaria Casciaro, Laura Minicucci, Daniele Roberto Giacobbe, Antonietta Martelli, Claudio Viscoli, Francesca Mattioli
This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography...
January 9, 2018: New Microbiologica
https://www.readbyqxmd.com/read/29297422/steady-state-pharmacokinetics-of-cycloserine-in-patients-on-terizidone-for-multidrug-resistant-tuberculosis
#5
R Court, L Wiesner, A Stewart, N de Vries, J Harding, G Maartens, T Gumbo, H McIlleron
SETTING: Terizidone/cycloserine (TRD/CS) is included in standard treatment regimens for multidrug-resistant tuberculosis (MDR-TB) in many countries. The steady state pharmacokinetics (PKs) of CS after TRD administration are not known. OBJECTIVES AND DESIGN: We recruited in-patients treated with 250-750 mg oral TRD daily as part of standard treatment regimens for pulmonary MDR-TB in Cape Town, South Africa. Plasma CS assays were performed in samples taken pre-dose and at 2, 4, 6, 8 and 10 h post-dose...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29290812/circulating-magnetic-microbubbles-for-localized-real-time-control-of-drug-delivery-by-ultrasonography-guided-magnetic-targeting-and-ultrasound
#6
Beata Chertok, Robert Langer
Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time...
2018: Theranostics
https://www.readbyqxmd.com/read/29280349/translational-model-to-predict-pulmonary-pharmacokinetics-and-efficacy-in-man-for-inhaled-bronchodilators
#7
Ramon Hendrickx, Eva Lamm Bergström, David L I Janzén, Markus Fridén, Ulf Eriksson, Ken Grime, Douglas Ferguson
Translational pharmacokinetic (PK) models are needed to describe and predict drug concentration-time profiles in lung tissue at the site of action to enable animal-to-man translation and prediction of efficacy in humans for inhaled medicines. Current pulmonary PK models are generally descriptive rather than predictive, drug/compound specific, and fail to show successful cross-species translation. The objective of this work was to develop a robust compartmental modeling approach that captures key features of lung and systemic PK after pulmonary administration of a set of 12 soluble drugs containing single basic, dibasic, or cationic functional groups...
December 27, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29277683/new-aerosol-formulation-to-control-ciprofloxacin-pulmonary-concentration
#8
Barbara Lamy, Frederic Tewes, Dolores Remedios Serrano, Isabelle Lamarche, Patrice Gobin, William Couet, Anne Marie Healy, Sandrine Marchand
Ciprofloxacin (CIP) apparent permeability across a pulmonary epithelium model can be controlled by the affinity of its complex with a metal cation. The higher the complex affinity, the larger is the reduction in CIP apparent permeability. The aim of this study was to evaluate if the control of the CIP apparent permeability observed in vitro could be transposed in vivo to control the CIP lung-to-blood absorption rate and CIP concentrations in the lung epithelial lining fluid (ELF) after intratracheal (IT) administration...
December 22, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29259743/discovery-of-bi-2545-a-novel-autotaxin-inhibitor-that-significantly-reduces-lpa-levels-in-vivo
#9
Christian A Kuttruff, Marco Ferrara, Tom Bretschneider, Stefan Hoerer, Sandra Handschuh, Bernd Nosse, Helmut Romig, Paul Nicklin, Gerald J Roth
In an effort to find new therapeutic interventions addressing the unmet medical need of patients with idiopathic pulmonary fibrosis, we initiated a program to identify new autotaxin (ATX) inhibitors. Starting from a recently published compound (PF-8380), we identified several highly potent ATX inhibitors with improved pharmacokinetic and safety profiles. Further optimization efforts resulted in the identification of a single-digit nanomolar lead compound (BI-2545) that shows substantial lowering of LPA in vivo and is therefore considered a valuable tool for further studies...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29239016/intestinal-and-hepatic-contributions-to-the-pharmacokinetic-interaction-between-gamithromycin-and-rifampicin-after-single-dose-and-multiple-dose-administration-in-healthy-foals
#10
S Berlin, S Wallstabe, E Scheuch, S Oswald, M Hasan, D Wegner, M Grube, M Venner, A Ullrich, W Siegmund
BACKGROUND: Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative...
December 14, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/29236967/postoperative-analgesia-after-pulmonary-resection-with-a-focus-on-video-assisted-thoracoscopic-surgery
#11
Marzia Umari, Valentina Carpanese, Valeria Moro, Gaia Baldo, Stefano Addesa, Enrico Lena, Stefano Lena, Umberto Lucangelo
Video-assisted thoracoscopic surgery is a widespread technique that has been linked to improved postoperative respiratory function, reduced hospital length of stay and a higher level of tolerability for the patients. Acute postoperative pain is of considerable significance, and the late development of neuropathic pain syndrome is also an issue. As anaesthesiologists, we have investigated the available evidence to optimize postoperative pain management. An opioid-sparing multimodal approach is highly recommended...
December 8, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29223508/on-the-pharmacokinetics-of-two-inhaled-budesonide-formoterol-combinations-in-asthma-patients-using-modeling-approaches
#12
K Soulele, P Macheras, V Karalis
Dry powder inhalers containing the budesonide/formoterol combination have currently a well-established position among other inhaled products. Even though their efficacy mainly depends on the local concentrations of the drug they deliver within the lungs, their safety profile is directly related to their total systemic exposure. The aim of the present investigation was to explore the absorption and disposition kinetics of the budesonide/formoterol combination delivered via two different dry powder inhalers in asthma patients...
December 6, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29217526/first-in-human-phase-i-study-of-single-agent-vanucizumab-a-first-in-class-bi-specific-anti-ang-2-anti-vegf-antibody-in-adult-patients-with-advanced-solid-tumors
#13
Manuel Hidalgo, Maria Martinez-Garcia, Christophe Le Tourneau, Christophe Massard, Elena Garralda, Valentina Boni, Alvaro Taus, Joan Albanell, Marie-Paule Sablin, Marie Alt, Rastilav Bahleda, Andreea Varga, Christophe Boetsch, Izolda Franjkovic, Florian Heil, Angelika Lahr, Katharina Lechner, Anthony Morel, Tapan K Nayak, Simona Rossomanno, Kevin Smart, Kay-Gunnar Stubenrauch, Oliver Krieter
PURPOSE: Vanucizumab is an investigational anti-angiogenic, first-in-class, bi-specific monoclonal antibody targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard therapies. EXPERIMENTAL DESIGN: Patients received escalating bi-weekly (q2w; 3-30 mg/kg) or weekly (qw; 10-30 mg/kg) intravenous doses guided by a Bayesian logistic regression model with overdose control...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29200281/discovery-and-optimization-of-thiazolidinyl-and-pyrrolidinyl-derivatives-as-inhaled-pde4-inhibitors-for-respiratory-diseases
#14
Laura Carzaniga, Gabriele Amari, Andrea Rizzi, Carmelida Capaldi, Renato De Fanti, Eleonora Ghidini, Gino Villetti, Chiara Carnini, Nadia Moretto, Fabrizio Facchinetti, Paola Caruso, Gessica Marchini, Loredana Battipaglia, Riccardo Patacchini, Valentina Cenacchi, Roberta Volta, Francesco Amadei, Alice Pappani, Silvia Capacchi, Valentina Bagnacani, Maurizio Delcanale, Paola Puccini, Silvia Catinella, Maurizio Civelli, Elisabetta Armani
Phosphodiesterase 4 (PDE4) is a key cAMP-metabolising enzyme involved in the pathogenesis of inflammatory disease and its pharmacological inhibition has been shown to exert therapeutic efficacy in chronic obstructive pulmonary disease (COPD). Herein we describe a drug discovery program aiming at the identification of novel classes of potent PDE4 inhibitors suitable for pulmonary administration. Starting from a previous series of benzoic acid esters, we explored the chemical space in the solvent-exposed region of the enzyme catalytic binding pocket...
December 4, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29197631/pulmonary-drug-delivery-to-older-people
#15
Martin Wallin, Tatsuaki Tagami, Lan Chen, Mingshi Yang, Hak-Kim Chan
Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are common in older people. Treatment principles are well established in this group of patients; however, inadequate training and improper inhaler techniques often results in poor treatment outcomes. Healthcare professionals often do not have the required knowledge about the most common inhaler devices. Age-related conditions like cognitive ability and physical strength would also impact on the inhaler usage. Pharmacokinetics and pharmacodynamics may be affected by physiological changes, like impaired renal and hepatic functions and reduced lung functions...
November 29, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29196412/a-phase-1-trial-of-vadastuximab-talirine-as-monotherapy-in-patients-with-cd33-positive-acute-myeloid-leukemia-aml
#16
Eytan M Stein, Roland B Walter, Harry P Erba, Amir T Fathi, Anjali S Advani, Jeffrey E Lancet, Farhad Ravandi, Tibor Kovacsovics, Daniel J DeAngelo, Dale Bixby, Stefan Faderl, Anand P Jillella, Phoenix Ho, Megan M O'Meara, Baiteng Zhao, Charles Biddle-Snead, Anthony S Stein
Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study (clinicaltrials.gov NCT01902329) evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naïve patients...
December 1, 2017: Blood
https://www.readbyqxmd.com/read/29189185/enhanced-both-in-vitro-and-in-vivo-kinetics-by-slns-induced-transdermal-system-of-furosemide-a-novel-approach
#17
Revathi Mannam, Indira Muzib Yallamalli
AIM AND BACKGROUND: Furosemide is a potent diuretic agent used to treat pulmonary arterial hypertension. Variable dosage regimen and poor pharmacokinetic parameters has led to the development of transdermal drug delivery system. A patent on suitability of multi-lamellar structures for excellent transdermal delivery (US 0367475A1) has encouraged us to formulate the solid lipid nanoparticles (SLNs) induced transdermal systems of furosemide to enhance the kinetic properties without incorporating any penetration enhancer and rate limiting polymers...
November 28, 2017: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/29188408/phase-ib-trial-of-the-anti-cancer-stem-cell-dll4-binding-agent-demcizumab-with-pemetrexed-and-carboplatin-as-first-line-treatment-of-metastatic-non-squamous-nsclc
#18
Mark J McKeage, Dusan Kotasek, Ben Markman, Manuel Hidalgo, Michael J Millward, Michael B Jameson, Dean L Harris, Robert J Stagg, Ann M Kapoun, Lu Xu, Brett G M Hughes
BACKGROUND: Delta-like ligand 4-Notch (DLL4-Notch) signaling contributes to the maintenance of chemotherapy-resistant cancer stem cells and tumor vasculature. OBJECTIVE: This phase IB trial of demcizumab, an IgG2 humanized monoclonal antibody directed against DLL4, was undertaken to determine its maximum tolerated dose, safety, immunogenicity, preliminary efficacy, pharmacokinetics, and pharmacodynamics, combined with standard chemotherapy. PATIENTS AND METHODS: Forty-six treatment-naive patients with metastatic non-squamous non-small cell lung cancer (NSCLC) were enrolled in this open-label, dose-escalation study using a standard 6 + 6 design...
November 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29186509/moxifloxacin-target-site-concentrations-in-patients-with-pulmonary-tb-utilizing-microdialysis-a-clinical-pharmacokinetic-study
#19
M Tobias Heinrichs, Sergo Vashakidze, Ketino Nikolaishvili, Irina Sabulua, Nestani Tukvadze, Nino Bablishvili, Shota Gogishvili, Brent P Little, Adam Bernheim, Jeannette Guarner, Charles A Peloquin, Henry M Blumberg, Hartmut Derendorf, Russell R Kempker
Background: Moxifloxacin is a second-line anti-TB drug that is useful in the treatment of drug-resistant TB. However, little is known about its target site pharmacokinetics. Lower drug concentrations at the infection site (i.e. in severe lung lesions including cavitary lesions) may lead to development and amplification of drug resistance. Improved knowledge regarding tissue penetration of anti-TB drugs will help guide drug development and optimize drug dosing. Methods: Patients with culture-confirmed drug-resistant pulmonary TB scheduled to undergo adjunctive surgical lung resection were enrolled in Tbilisi, Georgia...
November 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29180863/paclitaxel-and-quercetin-nanoparticles-co-loaded-in-microspheres-to-prolong-retention-time-for-pulmonary-drug-delivery
#20
Kang Liu, Weijuan Chen, Tingting Yang, Baofang Wen, Dejun Ding, Michael Keidar, Jinbao Tang, Weifen Zhang
High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery...
2017: International Journal of Nanomedicine
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