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Pulmonary pharmacokinetics

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https://www.readbyqxmd.com/read/29133080/population-pharmacokinetics-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#1
Ulrike Schmid, Christiane Doege, Claudia Dallinger, Matthias Freiwald
BACKGROUND: Nintedanib is a potent intracellular inhibitor of tyrosine kinases, including the receptor kinases vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor. A previous model assessed the population pharmacokinetics of nintedanib and its main metabolite BIBF 1202 in patients with non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). The objective of this analysis was to further characterise the population pharmacokinetics of nintedanib in patients with IPF by including data from the Phase III trials...
November 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29129557/pharmacokinetic-and-behavioural-profile-of-thc-cbd-and-thc-cbd-combination-after-pulmonary-oral-and-subcutaneous-administration-in-rats-and-confirmation-of-conversion-in-vivo-of-cbd-to-thc
#2
Tomáš Hložek, Libor Uttl, Lukáš Kadeřábek, Marie Balíková, Eva Lhotková, Rachel R Horsley, Pavlína Nováková, Klára Šíchová, Kristýna Štefková, Filip Tylš, Martin Kuchař, Tomáš Páleníček
Metabolic and behavioural effects of, and interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are influenced by dose and administration route. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous (sc.) THC, CBD and THC+CBD. Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD in serum and brain were determined over 24h, locomotor activity (open field) and sensorimotor gating (prepulse inhibition, PPI) were also evaluated. In line with recent knowledge we expected metabolic and behavioural interactions between THC and CBD...
November 9, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29121645/novel-lung-imaging-biomarkers-and-skin-gene-expression-subsetting-in-dasatinib-treatment-of-systemic-sclerosis-associated-interstitial-lung-disease
#3
Viktor Martyanov, Grace-Hyun J Kim, Wendy Hayes, Shuyan Du, Bishu J Ganguly, Oumar Sy, Sun Ku Lee, Galina S Bogatkevich, Gary L Schieven, Elena Schiopu, Roberta Gonçalves Marangoni, Jonathan Goldin, Michael L Whitfield, John Varga
BACKGROUND: There are no effective treatments or validated clinical response markers in systemic sclerosis (SSc). We assessed imaging biomarkers and performed gene expression profiling in a single-arm open-label clinical trial of tyrosine kinase inhibitor dasatinib in patients with SSc-associated interstitial lung disease (SSc-ILD). METHODS: Primary objectives were safety and pharmacokinetics. Secondary outcomes included clinical assessments, quantitative high-resolution computed tomography (HRCT) of the chest, serum biomarker assays and skin biopsy-based gene expression subset assignments...
2017: PloS One
https://www.readbyqxmd.com/read/29119292/population-pharmacokinetics-of-nintedanib-an-inhibitor-of-tyrosine-kinases-in-patients-with-non-small-cell-lung-cancer-or-idiopathic-pulmonary-fibrosis
#4
Ulrike Schmid, Karl-Heinz Liesenfeld, Angele Fleury, Claudia Dallinger, Matthias Freiwald
PURPOSE: A population pharmacokinetic model was developed for nintedanib in patients with non-small cell lung cancer (NSCLC) or idiopathic pulmonary fibrosis (IPF). The effects of intrinsic and extrinsic patient factors on exposure of nintedanib and its main metabolite BIBF 1202 were studied. METHODS: Data from 1191 patients with NSCLC (n = 849) or IPF (n = 342) treated with oral nintedanib (once- or twice-daily, dose range 50-250 mg) in 4 Phase II or III studies were combined...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29119207/anesthesia-in-a%C3%A2-child-with-suspected-peroxisomal-disorder
#5
J S Englbrecht, M Maas
We present the case of an 8‑year-old female child with suspected peroxisomal disorder requiring general anesthesia for adenotomy, paracentesis and brainstem-evoked response audiometry. Peroxisomes are small intracellular organelles that catalyse key metabolic reactions. Peroxisomal disorders are a heterogeneous group of rare genetic diseases. Anesthesia can be challenging as adrenal insufficiency, mental retardation, muscle weakness, risk of pulmonary aspiration, airway complications, seizure disorders and altered pharmacokinetics and pharmacodynamics can occur in these patients but guidelines for anesthesia do not exist due to the heterogeneity and rarity of these diseases and case reports are rare...
November 8, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/29112326/real-world-challenges-and-unmet-needs-in-the-diagnosis-and-treatment-of-suspected-invasive-pulmonary-aspergillosis-in-patients-with-hematological-diseases-an-illustrative-case-study
#6
Martin Hoenigl, Juergen Prattes, Peter Neumeister, Albert Wölfler, Robert Krause
Recent years have seen important advances in the diagnosis of invasive pulmonary aspergillosis (IPA), complemented by the introduction of new therapies. Despite this, IPA remains a major cause of infection-related mortality in patients with hematological diseases. There are two main reasons for this. First, diagnosis of IPA remains a challenge, since risk factors and the clinical, radiological and mycological presentations vary not only by fungal disease stage, but also by patient group (e.g. neutropenic versus non-neutropenic patients)...
November 7, 2017: Mycoses
https://www.readbyqxmd.com/read/29106740/pharmacokinetics-of-nintedanib-in-subjects-with-hepatic-impairment
#7
Kristell Marzin, Gunther Kretschmar, Doreen Luedtke, Sandrine Kraemer, Raimund Kuelzer, Rozsa Schlenker-Herceg, Ulrike Schmid, David Schnell, Claudia Dallinger
Nintedanib is an intracellular inhibitor of tyrosine kinases used in the treatment of non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). This phase 1 open-label study investigated the influence of mild and moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of nintedanib following oral administration of a single 100-mg dose. Subjects with hepatic impairment classified as Child-Pugh A (mild hepatic impairment) or Child-Pugh B (moderate hepatic impairment) were eligible...
November 6, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29103924/ceftaroline-pharmacokinetics-and-pharmacodynamics-in-patients-with-cystic-fibrosis
#8
Emily E Barsky, Luis M Pereira, Keri J Sullivan, Alanna Wong, Alexander J McAdam, Gregory S Sawicki, Gregory P Priebe, Susan M Goobie
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent pathogen in patients with cystic fibrosis (CF) associated with increased morbidity. Ceftaroline fosamil is an intravenous (IV) cephalosporin with activity against MRSA. There are minimal data regarding dosing in the CF population. The objective of this study was to determine the pharmacokinetic and pharmacodynamic profile of IV ceftaroline in patients with CF. METHODS: We conducted a single-center prospective study of children and young adults with CF receiving ceftaroline (15mg/kg IV up to 600mg every 8h) as part of treatment for a CF pulmonary exacerbation between June 2016 and April 2017...
November 2, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/29079338/advances-in-experimental-and-mechanistic-computational-models-to-understand-pulmonary-exposure-to-inhaled-drugs
#9
Per Bäckman, Sumit Arora, William Couet, Ben Forbes, Wilbur de Kruijf, Amrit Paudel
Prediction of local exposure following inhalation of a locally acting pulmonary drug is central to the successful development of novel inhaled medicines, as well as generic equivalents. This work provides a comprehensive review of the state of the art with respect to multiscale computer models designed to provide a mechanistic prediction of local and systemic drug exposure following inhalation. The availability and quality of underpinning in vivo and in vitro data informing the computer based models is also considered...
October 25, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29076375/pulmonary-disposition-and-pharmacokinetics-of-minocycline-in-adult-horses
#10
Kate O Echeverria, Kara M Lascola, Steeve Giguère, Jonathan H Foreman, Scott A Austin
OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration. ANIMALS 7 healthy adult horses. PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL cells...
November 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/29063794/critical-physicochemical-and-biological-attributes-of-nanoemulsions-for-pulmonary-delivery-of-rifampicin-by-nebulization-technique-in-tuberculosis-treatment
#11
Kifayatullah Shah, Lai Wah Chan, Tin Wui Wong
The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29060463/development-of-a-physiologically-based-pharmacokinetic-model-of-paraquat
#12
Manupat Lohitnavy, Arnon Chitsakhon, Kritsada Jomprasert, Ornrat Lohitnavy, Brad Reisfeld
Paraquat (N, N'-dimethyl-4,4'-bipyridium dichloride) is a potent and widely used herbicide in agricultural countries, including Thailand. The presence of this chemical in the body can lead to toxic effects in the liver, kidney, and lung. Pulmonary toxicity has been identified as the main cause of acute toxicity in animals and humans. Chronic exposure to paraquat is associated with Parkinson's disease in humans. Paraquat is transported into the lungs by neutral amino acid transporter. Therefore, a physiologically based pharmacokinetic (PBPK) model of paraquat was developed with a description of the protein transporter mechanism...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29057472/pharmacokinetics-of-furosemide-administered-4-and-24%C3%A2-hours-prior-to-high-speed-exercise-in-horses
#13
H K Knych, A Vale, W D Wilson, P H Kass, R M Arthur, J H Jones
Furosemide is a diuretic agent used commonly in racehorses to attenuate the bleeding associated with exercise-induced pulmonary hemorrhage (EIPH). The current study describes serum and urine concentrations and the pharmacokinetics of furosemide following administration at 4 and 24 hrs prior to maximal exercise. Eight exercised adult Thoroughbred horses received a single IV administration of 250 mg of furosemide at 4 and 24 hrs prior to maximal exercise on a high-speed treadmill. Blood and urine samples were collected at time 0 and at various times for up to 72 hrs and furosemide concentrations determined using liquid chromatography-tandem mass spectrometry...
October 22, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29043538/venous-thromboembolism-prophylaxis-in-medically-ill-patients-a-mixed-treatment-comparison-meta-analysis
#14
REVIEW
Majed S Al Yami, Matthew A Silva, Jennifer L Donovan, Abir O Kanaan
The American College of Chest Physicians guidelines recommend unfractionated heparin (UFH), low molecular weight heparins (LMWHs) or fondaparinux for prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in medically-ill patients. Direct oral anticoagulants (DOACs) have been evaluated relative to enoxaparin for VTE prophylaxis though head-to-head comparisons of these agents are lacking. Therefore, we conducted a mixed treatment comparisons meta-analysis to evaluate the safety and efficacy of established treatments and DOACs for VTE prophylaxis in medically-ill patients...
October 17, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29037039/synthesis-and-preclinical-evaluation-of-18-f-peg3-fpn-for-the-detection-of-metastatic-pigmented-melanoma
#15
Xiaodong Xu, Lujie Yuan, Lianglan Yin, Yaqun Jiang, Yongkang Gai, Qingyao Liu, Yichun Wang, Yongxue Zhang, Xiaoli Lan
Although (18)F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide ((18)F-5-FPN) is considered a promising radiopharmaceutical for PET imaging of melanoma, it accumulates at high concentrations in the liver. The aim in this research was to optimize the structure of (18)F-5-FPN with triethylene glycol to reduce liver uptake as well as improve pharmacokinetics, and to evaluate its performance in detection of melanoma liver and lung metastases. (18)F-PEG3-FPN was successfully prepared with a high radiolabeling yield (44...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28994740/antibacterial-and-antitubercular-activities-of-cinnamylideneacetophenones
#16
Carlos R Polaquini, Guilherme S Torrezan, Vanessa R Santos, Ana C Nazaré, Débora L Campos, Laíza A Almeida, Isabel C Silva, Henrique Ferreira, Fernando R Pavan, Cristiane Duque, Luis O Regasini
Cinnamaldehyde is a natural product with broad spectrum of antibacterial activity. In this work, it was used as a template for design and synthesis of a series of 17 cinnamylideneacetophenones. Phenolic compounds 3 and 4 exhibited MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 77.9 to 312 µM against Staphylococcus aureus, Streptococcus mutans, and Streptococcus sanguinis. Compounds 2, 7, 10, and 18 presented potent effects against Mycobacterium tuberculosis (57...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28992055/amphotericin-b-concentrations-in-healthy-mallard-ducks-anas-platyrhynchos-following-a-single-intratracheal-dose-of-liposomal-amphotericin-b-using-an-atomizer
#17
Ashley Phillips, Christine V Fiorello, Rachel M Baden, Jack H Liu, Nathaniel C Burmas, Carlos A Ruvalcaba, Roger Monroy, F Charles Mohr, Ronette Gehring, Jean-Pierre Delplanque, Karl V Clemons, David A Stevens, Lisa A Tell
Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. The objective of this study was to evaluate if a single 3 mg/kg dose of liposomal amphotericin B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhibitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos)...
August 3, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28987804/pharmacodynamics-pharmacokinetics-and-safety-of-revefenacin-td-4208-a-long-acting-muscarinic-antagonist-in-patients-with-chronic-obstructive-pulmonary-disease-copd-results-of-two-randomized-double-blind-phase-2-studies
#18
Dean Quinn, Christopher N Barnes, Wayne Yates, David L Bourdet, Edmund J Moran, Peter Potgieter, Andrew Nicholls, Brett Haumann, Dave Singh
BACKGROUND: Revefenacin (TD-4208) is a potent, lung-selective, long-acting muscarinic antagonist currently in development for once-daily treatment of chronic obstructive pulmonary disease (COPD). We evaluated the pharmacodynamics (bronchodilator activity), pharmacokinetics (PK) and safety of single- and multiple-dose administrations of nebulized revefenacin in two clinical trials (Study 0059 and Study 0091) in patients with moderate to severe COPD. METHODS: In Study 0059, 32 patients were randomized to receive a single dose of revefenacin (350 or 700 μg), active control ipratropium (500 μg) or placebo inhalation solution administered via standard jet nebulizer in a double-blind, crossover fashion...
October 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28928173/cohort-profile-of-a-study-on-outcomes-related-to-tuberculosis-and-antiretroviral-drug-concentrations-in-uganda-design-methods-and-patient-characteristics-of-the-south-study
#19
Christine Sekaggya-Wiltshire, Barbara Castelnuovo, Amrei von Braun, Joseph Musaazi, Daniel Muller, Allan Buzibye, Ursula Gutteck, Lars Henning, Bruno Ledergerber, Natascia Corti, Mohammed Lamorde, Jan Fehr, Andrew Kambugu
PURPOSE: Tuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes. PARTICIPANTS: Patients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on first-line anti-TB treatment...
September 18, 2017: BMJ Open
https://www.readbyqxmd.com/read/28922811/a-programme-to-create-short-course-chemotherapy-for-pulmonary-mycobacterium-avium-disease-based-on-pharmacokinetics-pharmacodynamics-and-mathematical-forecasting
#20
Devyani Deshpande, Shashikant Srivastava, Tawanda Gumbo
Objectives: Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. Methods: We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016...
September 1, 2017: Journal of Antimicrobial Chemotherapy
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