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There are few studies in humans dealing with the relationship between physico-chemical properties of drugs and their systemic bioavailability after administration via oral inhalation route (Fpulm). Getting further insight in the determinants of Fpulm after oral pulmonary inhalation could be of value for drugs considered for a systemic delivery as a result of poor oral bioavailability, as well as for drugs considered for a local delivery to anticipate their undesirable systemic effects. To better delineate the parameters influencing the systemic delivery after oral pulmonary inhalation in humans, we studied the influence of physico-chemical and permeability properties obtained in silico on the rate and extent of Fpulm in a series of 77 compounds with or without marketing approval for pulmonary delivery, and intended either for local or for systemic delivery. Principal component analysis (PCA) showed mainly that Fpulm was positively correlated with Papp and negatively correlated with %TPSA, without a significant influence of solubility and ionization fraction, and no apparent link with lipophilicity and drug size parameters. As a result of the small sample set, the performance of the different models as predictive of Fpulm were quite average with random forest algorithm displaying the best performance. As a whole, the different models captured between 50 and 60% of the variability with a prediction error of less than 20%. Tmax data suggested a significant positive influence of lipophilicity on absorption rate while charge apparently had no influence. A significant linear relationship between Cmax and dose (R = "0.79) highlighted that Cmax was primarily dependent on dose and absorption rate and could be used to estimate Cmax in humans for new inhaled drugs.
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http://dx.doi.org/10.1016/j.ejpb.2021.04.014 | DOI Listing |
J Int Med Res
December 2024
Department of Pediatrics, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabi.
Objective: Duchenne muscular dystrophy (DMD) is a rare X-linked neurodegenerative disorder caused by mutations in the gene. This study examined the efficacy and safety of ataluren, the first oral treatment for DMD with nonsense mutations (nmDMD), in patients in the Middle East.
Methods: This retrospective longitudinal study assessed the outcomes of seven boys with nmDMD who received treatment with ataluren and follow-up at a single center since 2016.
Lung India
January 2025
UOC Pneumologia, Ospedale San Filippo Neri-ASL Roma 1, Rome, Italy.
The burden of autoimmune diseases is rising worldwide. The expansion of the population of patients eligible for severe asthma biological therapy we are seeing in clinical practice could lead to the simultaneous use of different monoclonal antibodies. We present the case of biological combination therapy with ustekinumab and benralizumab in a patient with ulcerative colitis and severe eosinophilic asthma.
View Article and Find Full Text PDFACS Appl Bio Mater
December 2024
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India.
Glucose-dependent insulin delivery systems have been recognized as a promising approach for controlling blood sugar levels in individuals with diabetes mellitus (DM). Recently, titanium dioxide nanoparticles have garnered huge attention in scientific research for their small size and effective drug delivery capabilities. In this study, we developed alizarin (AL)-capped phenylboronic acid (PBA)-functionalized titanium dioxide nanoparticles (TiO) for glucose-sensitive insulin delivery (TiO-PBA-INS-AL) aiming to manage both blood sugar levels and its associated organ pathology in DM.
View Article and Find Full Text PDFCureus
November 2024
General Surgery, Brookdale University Hospital Medical Center, New York, USA.
and are anaerobic bacteria rarely encountered in clinical practice, making their identification in bacteremia significant. These organisms are typically found in the human gut and oral flora and are generally considered low-virulence. However, in patients with compromised immunity or significant comorbidities, they can lead to severe infections, including bacteremia.
View Article and Find Full Text PDFAm J Case Rep
December 2024
Department of Thoracic Surgery, Linyi People's Hospital, Linyi, Shandong, China.
BACKGROUND ROS1 fusion-positive locally-advanced lung adenocarcinoma is a rare malignant tumor with no clear neoadjuvant therapy guidelines and a poor prognosis. This report describes a 49-year-old man with a ROS1 fusion-positive locally-advanced lung adenocarcinoma with a pathological complete response (pCR) to the tyrosine kinase inhibitor crizotinib combined with chemotherapy. CASE REPORT A 49-year-old Chinese man visited the hospital with a cough and phlegm that began over 20 days ago.
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