Praziquantel has been the mainstay of schistosomiasis control since 1984 and widely distributed since 2006 through 'preventive chemotherapy' programmes to school-aged children or at-risk populations. In addition, preschool-aged children are now recognized as a vulnerable population and a group for targeted treatment, but they may be difficult to dose correctly with the available product--a racemate, based on the biologically active enantiomer (R-praziquantel) and the inactive distomer (S-praziquantel), which contributes the bitter taste and doubles the size of the tablets. Hence, a paediatric formulation is required, possibly enantiomerically pure. Developing such a product and extending its use to younger children should be pharmacologically guided, but limited data exist on pharmacokinetics and pharmacokinetic/pharmacodynamic correlations for praziquantel. This article presents available data on the chemistry, pharmacokinetics and pharmacodynamics of praziquantel, as well as R-praziquantel, and points to gaps in our knowledge.
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http://dx.doi.org/10.1093/jac/dkt491 | DOI Listing |
Int J Nanomedicine
January 2025
School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
Purpose: To improve the oral absorption of relugolix (RLGL), which has low oral bioavailability due to its low solubility and being a substrate of P-glycoprotein (P-gp). A solid self-microemulsifying drug delivery system of relugolix (RLGL-S-SMEDDS) was prepared and evaluated in vitro and in vivo.
Methods: The composition of the solid self-microemulsifying drug delivery system (S-SMEDDS) was selected by solubility study and pseudo-ternary phase diagram, and further optimized by Design-Expert optimization design.
BMJ Oncol
May 2024
Sarah Cannon Cancer Institute, Nashville, Tennessee, USA.
Objective: The arginase inhibitor INCB001158 was evaluated for safety (primary endpoint) in locally advanced or metastatic solid tumours; pharmacokinetics, pharmacodynamics and efficacy were also assessed.
Methods And Analysis: In this non-randomised, open-label, three-part phase 1 study, INCB001158 was orally administered two times per day as monotherapy or in combination with intravenous pembrolizumab 200 mg every 3 weeks. Dose expansion was conducted in tumour-type cohorts (with or without prior anti-PD-1/PD-L1 (programmed death protein 1/programmed death ligand 1) therapy).
J Biomed Opt
January 2025
Lund University, Department of Physics, Lund, Sweden.
Significance: The spatial distribution of the photosensitizing drug concentration is an important parameter for predicting the photodynamic therapy (PDT) outcome. Current diffuse fluorescence tomography methods lack accuracy in quantifying drug concentration. The development of accurate methods for monitoring the temporal evolution of the drug distribution in tissue can advance the real-time light dosimetry in PDT of tumors, leading to better treatment outcomes.
View Article and Find Full Text PDFFront Vet Sci
January 2025
Department of Zoology, Abdul Wali Khan University, Mardan, Khyber Pakhtunkhwa, Pakistan.
, responsible for flea-borne spotted fever, is a rising zoonotic pathogen posing an increasing global threat due to its expanding geographical distribution. The rise in antibiotic-resistant strains of this pathogen underscores the urgent need for new therapeutic interventions. This study employed a comprehensive subtractive proteomics analysis of the proteome, aiming to identify essential, non-host homologous, and pathogen-specific proteins, which were subsequently evaluated as potential new drug targets.
View Article and Find Full Text PDFJ Med Chem
January 2025
Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai 201203, China.
Fibroblast growth factor receptors (FGFRs) are established oncogenic drivers in various solid tumors. However, the approved FGFR inhibitors face challenges with acquired resistance and dose-limiting adverse effects associated with FGFR1/4 inhibition, limiting therapeutic efficacy. Herein, we systematically explored linker and electrophile moieties based on the pyrrolopyrazine carboxamide core and identified aniline α-fluoroacrylamide as an effective covalent warhead.
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