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Whole-Body Physiologically Based Pharmacokinetic Modeling of GalNAc-Conjugated siRNAs.
Pharmaceutics
January 2025
Department of Pharmaceutical Bioscience, Translational Drug Discovery and Development, Uppsala University, SE-75124 Uppsala, Sweden.
: N-acetyl-galactosamine small interfering RNAs (GalNAc-siRNA) are an emerging class of drugs due to their durable knockdown of disease-related proteins. Direct conjugation of GalNAc onto the siRNA enables targeted uptake into hepatocytes via GalNAc recognition of the Asialoglycoprotein Receptor (ASGPR). With a transient plasma exposure combined with a prolonged liver half-life, GalNAc-siRNA exhibits distinct disposition characteristics.
View Article and Find Full Text PDFPK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance.
Antibiotics (Basel)
January 2025
Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo 693-8501, Shimane, Japan.
Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, focusing on three key aspects.
View Article and Find Full Text PDFActivity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020-2022).
BMC Pulm Med
January 2025
Element Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A North Liberty, Iowa, IA, 52317, USA.
Background: Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals.
Methods: Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory.
Impact of attaining an aggressive PK/PD target with continuous infusion beta-lactams on the clinical efficacy of targeted therapy of early post-transplant Gram-negative infections in critically ill OLT recipients. An interim analysis of a 3-year prospective, observational, study.
J Infect Dis
January 2025
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy.
Background: To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections.
Methods: OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured.
Background: Antibody-drug conjugate (ADC) is an anticancer drug that links toxins to specifically targeted antibodies via linkers, offering the advantages of high target specificity and high cytotoxicity. However, complexity of its structural composition poses a greater difficulty for drug design studies.
Objectives: Pharmacokinetic/pharmacodynamic (PK/PD) based consideration of ADCs has increasingly become a hot research topic for optimal drug design in recent years, providing possible ideas for obtaining ADCs with desirable properties.
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