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Pulmonary pharmacokinetics

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https://www.readbyqxmd.com/read/28099979/milrinone-pharmacokinetics-and-pharmacodynamics-in-neonates-with-persistent-pulmonary-hypertension-of-the-newborn
#1
Annie Giaccone, Athena F Zuppa, Beena Sood, Meryl S Cohen, Michael L O'Byrne, Ganesh Moorthy, Amit Mathur, Haresh Kirpalani
Objective To describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition. Design Randomized, open label pilot study. Setting Multicenter; level 3 and level 4 neonatal intensive care units. Patients Six infants ≥34 weeks' gestational age and <10 days of life with persistent hypoxemia receiving inhaled nitric oxide. Intervention Intravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0...
January 18, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28095918/anti-staphylococcal-activity-resulting-from-epithelial-lining-fluid-elf-concentrations-of-amikacin-inhale-administered-via-the-pulmonary-drug-delivery-system
#2
Islam M Ghazi, Mordechai Grupper, David P Nicolau
BACKGROUND: Amikacin inhale (BAY41-6551), a unique drug-device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as Pseudomonas aeruginosa and the Enterobacteriaceae, Staphylococcus aureus is increasingly recognized as a pathogen of concern for these pulmonary based infections...
January 17, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28092695/absorption-distribution-and-excretion-of-the-anti-tuberculosis-drug-delamanid-in-rats-extensive-tissue-distribution-suggests-potential-therapeutic-value-for-extrapulmonary-tuberculosis
#3
Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara
Delamanid (OPC-67683, Deltyba(TM) , nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution, and excretion of delamanid-derived radioactivity were investigated after a single oral administration of (14) C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 hours postdose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma...
January 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28089914/arachidonic-acid-with-taurine-enhances-pulmonary-absorption-of-macromolecules-without-any-serious-histopathological-damages
#4
Masateru Miyake, Takanori Minami, Hiroyuki Yamazaki, Chie Emoto, Tadashi Mukai, Hajime Toguchi
Therapeutic peptides and protein are being used in several indications; however, their poor permeability still remains to be solved. This study focused on the pulmonary route of macromolecules. First, the effects of arachidonic acid (AA) as an absorption enhancer on drug serum concentration, after intratracheal administration, were investigated in rats. Second, the safety of AA was assessed in rats in an acute toxicity study for 7 days. AA enhanced the exposure of both interferon-α (IFN-α) and fluorescein isothiocyanate 4000 (FD-4)...
January 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28078552/pediatric-development-of-bosentan-facilitated-by-modeling-and-simulation
#5
Jochen Zisowsky, Martine Géhin, Andjela Kusic-Pajic, Andreas Krause, Maurice Beghetti, Jasper Dingemanse
BACKGROUND: Bosentan is approved for use in adult patients with pulmonary arterial hypertension. The primary aim of the pharmacokinetic modeling was the provision of a systematic guidance for study design and enhanced understanding of pharmacokinetics across the entire pediatric age range. METHODS: A physiologically based pharmacokinetic model was developed for the pediatric population; starting from an adult model, the effects of body weight, age, and maturation of relevant metabolizing enzymes were incorporated to extrapolate the pharmacokinetics to children...
January 11, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28074294/-procedures-on-patients-receiving-noacs-what-s-possible
#6
A Polzin, M Kelm, P Horn
Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and atrial fibrillation (AF). However, there is insufficient data concerning the periinterventional, perioperative, and intensive care management of patients on NOACs. Therefore, the recommendations regarding this management rely on pharmacokinetics of the particular NOAC in combination with the individual patient's characteristics, bleeding risk of the planned intervention/surgery, and urgency of the procedure...
January 10, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28063154/pharmacological-indices-and-pulmonary-distribution-of-rifampicin-after-repeated-oral-administration-in-healthy-foals
#7
S Berlin, A Kirschbaum, L Spieckermann, S Oswald, M Keiser, M Grube, M Venner, W Siegmund
BACKGROUND: The treatment of equine lung infections by R. equi with rifampicin is empirically based because pharmacokinetic/pharmacodynamic (PK/PD) indices and pivotal clinical outcome data are not available. OBJECTIVES: Evaluation of pharmacokinetics and pulmonary distribution into epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALC) to predict antimicrobial activity in the lung using PK/PD-indices. STUDY DESIGN: Controlled, randomised, two-period, crossover, repeated-dose study with an initial arm to measure disposition after intravenous administration...
January 7, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28061907/a-randomized-seven-day-study-to-assess-the-efficacy-and-safety-of-a-glycopyrrolate-formoterol-fumarate-fixed-dose-combination-metered-dose-inhaler-using-novel-co-suspension%C3%A2-delivery-technology-in-patients-with-moderate-to-very-severe-chronic-obstructive-pulmonary
#8
Colin Reisner, Leonardo M Fabbri, Edward M Kerwin, Charles Fogarty, Selwyn Spangenthal, Klaus F Rabe, Gary T Ferguson, Fernando J Martinez, James F Donohue, Patrick Darken, Earl St Rose, Chad Orevillo, Shannon Strom, Tracy Fischer, Michael Golden, Sarvajna Dwivedi
BACKGROUND: Long-acting muscarinic antagonist/long-acting β2-agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI). METHODS: This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD ( NCT01085045 )...
January 6, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28061018/bronchopulmonary-pharmacokinetics-of-r-salbutamol-and-s-salbutamol-enantiomers-in-pulmonary-epithelial-lining-fluid-and-lung-tissue-of-horses
#9
Glenn A Jacobson, Sharanne Raidal, Kate Robson, Christian K Narkowicz, David S Nichols, E Haydn Walters
AIMS: Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing. METHODS: Horses (n = 12) received racemic (rac-) salbutamol 1000 microgram via inhalation. Enantioselective UPLC-MS/MS was used to determine salbutamol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in central lung (endoscopic bronchial biopsy) and peripheral lung (percutaneous pulmonary biopsy) tissues (at 20 and 25 minutes respectively), and in plasma samples...
January 6, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28039077/pharmacokinetics-of-tiotropium-administered-by-respimat-%C3%A2-in-asthma-patients-analysis-of-pooled-data-from-phase-ii-and-iii-clinical-trials
#10
Ashish Sharma, Huib A M Kerstjens, René Aalbers, Petra Moroni-Zentgraf, Benjamin Weber, Ronald Dahl
Tiotropium is a long-acting inhaled antimuscarinic bronchodilator that has recently received marketing authorization for the indication of asthma with dose delivery via the Respimat(®) inhaler, in addition to its widely established role in the management of chronic obstructive pulmonary disease (COPD). This report presents a combined analysis of tiotropium plasma and urine pharmacokinetics at steady state from 8 Phase II/III clinical trials in asthma and delineates the effects of patient characteristics on systemic exposure based on the parameters fe0-24,ss (fraction of dose excreted unchanged in urine over 24 h post-dose at steady-state) and dose-normalized AUCtau,ss and Cmax,ss...
December 27, 2016: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28032910/effect-of-everolimus-on-the-pharmacokinetics-of-octreotide-long-acting-repeatable-in-patients-with-advanced-neuroendocrine-tumors-an-analysis-of-the-randomized-phase-iii-radiant-2-trial
#11
M E Pavel, C Becerra, K Grosch, W Cheung, J Hasskarl, J C Yao
In the RADIANT-2 trial, addition of everolimus to octreotide long-acting repeatable (LAR) exhibited a clinically meaningful 5.1-month improvement in progression-free survival (PFS) in patients with advanced functional neuroendocrine tumors. In this study, we characterized the effects of everolimus co-administration on octreotide LAR pharmacokinetics and its relationship with efficacy and safety. At least one evaluable blood everolimus and plasma octreotide predose minimum concentration (Cmin ) was available for 182 patients and 294 patients, respectively...
November 7, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28031207/pharmacokinetics-pharmacodynamics-of-pulmonary-delivery-of-colistin-against-pseudomonas-aeruginosa-in-a-mouse-lung-infection-model
#12
Yu-Wei Lin, Qi Tony Zhou, Soon-Ee Cheah, Jinxin Zhao, Ke Chen, Jiping Wang, Hak-Kim Chan, Jian Li
Colistin is often administered by inhalation and/or parenteral route for the treatment of respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa However, limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to guide the optimization of dosage regimens of inhaled colistin. In the present study, PK of colistin in epithelial lining fluid (ELF) and plasma was determined following intra-tracheal delivery of a single dose of colistin solution in neutropenic lung-infected mice...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28029509/renal-function-and-venous-thromboembolic-diseases
#13
N Janus, I Mahé, V Launay-Vacher, J-P Laroche, G Deray
Anticoagulant agents have been approved by international regulatory agencies to prevent and treat venous thromboembolism (VTE). However, chronic kidney disease (CKD) is: (1) highly frequent in VTE patients; (2) strongly linked to VTE; and (3) a risk factor for cardiovascular morbidity/mortality and fatal pulmonary embolism. Therefore, an increasing number of patients are presented with CKD and VTE and more and more physicians must face the questions of the management of these patients and that of the handling of anticoagulant agents in CKD patients because of the pharmacokinetic modifications of these drugs in this population...
October 28, 2016: Journal des Maladies Vasculaires
https://www.readbyqxmd.com/read/28013355/effect-of-sildenafil-on-the-activity-of-some-antidepressant-drugs-and-electroconvulsive-shock-treatment-in-the-forced-swim-test-in-mice
#14
Katarzyna Socała, Dorota Nieoczym, Elżbieta Wyska, Piotr Wlaź
Sildenafil, a potent and selective inhibitor of phosphodiesterase type 5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. It is often taken by patients suffering from depression and receiving antidepressant drug treatment. However, its influence on the efficacy of antidepressant treatment was not sufficiently studied. Therefore, the aim of the present study was to investigate the influence of sildenafil on the anti-immobility action of several antidepressant drugs (i.e...
December 24, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28012206/uptake-and-efflux-kinetics-and-intracellular-activity-of-voriconazole-against-a-fumigatus-in-human-pulmonary-epithelial-cells-a-new-application-for-the-prophylaxis-and-early-treatment-of-invasive-pulmonary-aspergillosis
#15
Taotao Wang, Qianting Yang, Lu Chen, Ying Li, Ti Meng, Yan Wang, Tao Zhang, Jin'e Lei, Jianfeng Xing, Yalin Dong
Invasive pulmonary aspergillosis (IPA), most caused by A. fumigatus, is a serious life-threating infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against A. fumigatus in A549 cells. High-performance liquid chromatography/tandem mass spectrometry and time-kill method was used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole...
December 23, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28007545/platinum-pharmacokinetics-in-mice-following-inhalation-of-cisplatin-dry-powders-with-different-release-and-lung-retention-properties
#16
Vincent Levet, Romain Merlos, Rémi Rosière, Karim Amighi, Nathalie Wauthoz
Pharmacokinetics of cisplatin administered by the pulmonary route were established in mice using dry powders inhaler (DPI) formulations showing immediate (F1) and controlled release (CR, solid lipid microparticles) in vitro, without (F2) or with PEGylated excipients (F3, F4). Formulation administration was realized using dry powder blends (correspondingly named thereafter F1B to F4B) able to reproducibly deliver particles in vivo using a DP-4M Dry Powder Insufflator™. Their platinum pharmacokinetics were established over 48h in lungs, total blood and non-target organs vs...
December 19, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27999290/validation-and-application-of-an-ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-yuanhuacine-determination-in-rat-plasma-after-pulmonary-administration-pharmacokinetic-evaluation-of-a-new-drug-delivery-system
#17
Man Li, Xiao Liu, Hao Cai, Zhichun Shen, Liu Xu, Weidong Li, Li Wu, Jinao Duan, Zhipeng Chen
Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to alleviate the adverse toxicity effects, we tried to deliver yuanhuacine directly into the lungs. Ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was used to detect the analyte and IS. After extraction (ether:dichloromethane = 8:1), the analyte and IS were separated on a Waters BEH-C18 column (100 mm × 2...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27990445/voriconazole-induced-periostitis-enthesopathy-in-solid-organ-transplant-patients-case-reports
#18
Monica Sircar, Camille Kotton, David Wojciechowski, Kassem Safa, Hannah Gilligan, Eliot Heher, Winfred Williams, Ravi Thadhani, Nina Tolkoff-Rubin
BACKGROUND: Voriconazole is frequently used to treat fungal infections in solid organ transplant patients. Recently, there have been reports suggesting that prolonged voriconazole therapy may lead to periostitis. AIM: Here we present two cases of voriconazole-induced periostitis in solid organ transplant patients. CASE PRESENTATION: Voriconazole was given to two transplant patients-one with a liver transplant and the second with a heart transplant, to treat their fungal infections...
November 2016: Journal of biosciences and medicines
https://www.readbyqxmd.com/read/27989858/aerosolizable-modified-release-particles-of-montelukast-improve-retention-and-availability-of-the-drug-in-the-lungs
#19
Brijeshkumar Patel, Jahidur Rashid, Fakhrul Ahsan
Montelukast, a cysteinyl leukotriene receptor antagonist available as oral tablets, is used as a second-line therapy in asthma. In this study, we sought to enhance the availability of montelukast in the lungs by encapsulating the drug in poly (lactide-co-glycolic acid)-based (PLGA) respirable large porous particles. We determined the oral and lung specific availability of montelukast by assessing metabolic stability of the drug in the lung and liver homogenates, respectively. We similarly measured the oral and inhalational bioavailability by monitoring the pharmacokinetics and disposition of the drug in live animals...
October 27, 2016: European Journal of Pharmaceutical Sciences
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
#20
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
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