14C-FCE 22101 was given intravenously to rats (4, 16 and 38 mg/kg), dogs (69 mg/kg), rabbits (99 mg/kg) and monkeys (41 and 99 mg/kg). Radioactivity was eliminated mainly in urine, with faecal excretion being less than 10% in all animal species. Radioactivity as expired 14CO2 was detected in the rat and accounted for less than 0.5% of the dose in 24 h. Tissue distribution was also investigated in the rat (38 mg/kg). After combustion and radioactivity counts the highest concentration of radioactivity was observed in the kidneys, followed by the lung, the skin and hair, and lastly by the liver and adrenals. Brain levels of radioactivity, corrected for blood contamination, were 40 to 60 times lower than the corresponding blood levels. The results of whole body autoradiography confirmed those above. Whole body autoradiography of pregnant rats did not show any transfer of radioactivity into fetuses and only low radioactivity was present in the placenta.
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http://dx.doi.org/10.1093/jac/23.suppl_c.165 | DOI Listing |
Front Pharmacol
December 2024
Holy Stone Healthcare, Preclinical and Development Div Hsinchu, Taipei, Taiwan.
Introduction: CA102N is a novel anticancer drug developed by covalently linking H-Nim (N-(4-Amino-2-phenoxyphenyl methanesulfonamide) to Hyaluronic Acid to target CD44 receptor-rich tumors. The proposed approach seeks to enhance the efficacy and overcome limitations associated with H-Nim, including poor solubility and short half-life.
Methods: The study aimed to evaluate the pharmacokinetics, biodistribution, metabolism, and tumor permeability of [14C] CA102N in xenograft mice following a single intravenous dose of 200 mg/kg.
PLoS One
December 2024
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Background: In tissue distribution studies of radiopharmaceuticals, quantitative whole-body autoradiography (QWBA) and oxidative combustion (OC) analysis are the two important methods that have not been compared using the same drug. Sprague-Dawley (SD) and Long-Evans (LE) rats, both of which are commonly used rodents in tissue distribution studies, have also not been compared using the same drug. Comparative studies are important for aiding the selection of appropriate experimental methods and animals.
View Article and Find Full Text PDFNucl Med Biol
November 2024
Amsterdam UMC location Vrije Universiteit Amsterdam, Dept Radiology & Nuclear Medicine, De Boelelaan 1117, Amsterdam, the Netherlands; Amsterdam Neuroscience, Brain Imaging, Amsterdam, the Netherlands. Electronic address:
Clin Transl Sci
October 2024
Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Yokohama-shi, Kanagawa, Japan.
The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss-Newton method (CGNM).
View Article and Find Full Text PDFACS Pharmacol Transl Sci
October 2024
CEA, INSERM, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, Université Paris-Saclay, 91400 Orsay, France.
We have previously developed seven fluorinated analogues of A-836339 as new PET tracers for cannabinoid type 2 receptor (CBR) imaging, among which ()--(3-(2-(2-[F]fluoroethoxy)ethyl)-4,5-dimethylthiazol-2(3)-ylidene)-2,2,3,3-tetramethylcyclopropane-1-carboxamide ([F]FC0324) displayed high affinity and selectivity for CBR in healthy rats. In the present study, we have further evaluated the imaging and metabolic properties of [F]FC0324 in a rat model of human CBR overexpression in the brain (AAV-CB) and in non-human primates (NHPs). Autoradiography with AAV-CB rat brain sections exhibited a signal of [F]FC0324 8-fold higher in the ipsilateral region than in the contralateral region.
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