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| http://dx.doi.org/10.1164/rccm.202402-0338VP | DOI Listing |
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Impact of genetic polymorphisms and drug-drug interactions mediated by carboxylesterase 1 on remimazolam deactivation.
Drug Metab Dispos
January 2025
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio. Electronic address:
Remimazolam (Byfavo, Acacia Pharma), a recent Food and Drug Administration-approved ester-linked benzodiazepine, offers advantages in sedation, such as rapid onset and predictable duration, making it suitable for broad anesthesia applications. Its favorable pharmacological profile is primarily attributed to rapid hydrolysis, the primary metabolism pathway for its deactivation. Thus, understanding remimazolam hydrolysis determinants is essential for optimizing its clinical use.
View Article and Find Full Text PDFUncovering the impact of COVID-19-mediated bidirectional dysregulation of cytochrome P450 3A4 on systemic and pulmonary drug concentrations using physiologically based pharmacokinetic modeling.
Drug Metab Dispos
January 2025
Current affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Current affiliation: OneDrug Inc., Toronto, Ontario, Canada; Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Centre for Applied Pharmacokinetic Research, School of Health Sciences, University of Manchester, Manchester, United Kingdom. Electronic address:
Several clinical studies have shown that COVID-19 increases the systemic concentration of drugs in hospitalized patients with COVID-19. However, it is unclear how COVID-19-mediated bidirectional dysregulation of hepatic and pulmonary cytochrome P450 (CYP) 3A4 affects drug concentrations, especially in the lung tissue, which is most affected by the disease. Herein, physiologically based pharmacokinetic modeling was used to demonstrate the differences in systemic and pulmonary concentrations of 4 respiratory infectious disease drugs when CYP3A4 is concurrently downregulated in the liver and upregulated in the lung based on existing clinical data on COVID-19-CYP3A4 interactions at varying severity levels including outpatients, non-intensive care unit (ICU), and ICU patients.
View Article and Find Full Text PDFSmart theranostic contact lenses.
J Control Release
January 2025
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea. Electronic address:
Although smart contact lenses have demonstrated great potential in theranostics, there remain critical challenges and opportunities in their commercial development. In this Perspective, the current status and capability of smart theranostic contact lenses are highlighted, focusing on their application as sensing systems for detecting biomarkers such as glucose, intraocular pressure (IOP), and inflammatory cytokines, and as drug delivery systems (DDS) for precise and controlled therapy. Additionally, key challenges associated with clinical development and commercialization of smart theranostic contact lenses are discussed, to optimize diagnostic and therapeutic interventions.
View Article and Find Full Text PDFEvaluating the efficacy of transcranial direct current stimulation (tDCS) in managing neuropathic pain-induced emotional consequences: Insights from animal models.
Neurophysiol Clin
January 2025
Université Marie et Louis Pasteur, INSERM, UMR 1322 LINC, F-25000 Besançon, France. Electronic address:
Neuropathic pain is a global health concern due to its severity and its detrimental impact on patients' quality of life. It is primarily characterized by sensory alterations, most commonly hyperalgesia and allodynia. As the disease progresses, patients with neuropathic pain develop co-occurring emotional disorders, such as anxiety and depression, which further complicate therapeutic management.
View Article and Find Full Text PDFTailoring anaesthetic strategies for diabetes research: Acepromazine vs. medetomidine in Aachen minipigs.
PLoS One
January 2025
Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Pre-established anaesthetic protocols in animal models might unexpectedly interfere with the main outcome of scientific projects and therefore they need to account for the specific research goals. We aimed to optimize the anaesthetic protocol and animal handling strategies in a diabetes-related-study exemplifying how the anaesthetic approach must be adjusted for individual research targets. Aachen minipigs were used as a model to test long-lasting skin glucose sensors for diabetic human patients.
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