Objective: Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species.
Animals: 6 healthy adult RTHA (3 males, 3 females) under human care.
Procedures: A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours.
Results: The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours.
Clinical Relevance: Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.
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http://dx.doi.org/10.2460/ajvr.21.10.0170 | DOI Listing |
PLoS One
January 2025
Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Muenster, Germany.
Weibel-Palade bodies (WPB) are secretory organelles exclusively found in endothelial cells and among other cargo proteins, contain the hemostatic von-Willebrand factor (VWF). Stimulation of endothelial cells results in exocytosis of WPB and release of their cargo into the vascular lumen, where VWF unfurls into long strings of up to 1000 µm and recruits platelets to sites of vascular injury, thereby mediating a crucial step in the hemostatic response. The function of VWF is strongly correlated to its structure; in order to fulfill its task in the vascular lumen, VWF has to undergo a complex packing/processing after translation into the ER.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
Pharmacy Department, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
Background: AUC-based dosing with validated Bayesian software is recommended as a good approach to guide bedside vancomycin dosing.
Objectives: To compare treatment and vancomycin-associated acute kidney injury (AKI) costs between Bayesian AUC-based dosing and conventional therapeutic drug monitoring (TDM) using steady-state plasma concentrations of vancomycin administered as continuous infusion in hospitalized non-critically ill patients with severe Gram-positive infection.
Methods: A cost-benefit analysis presented as a return on investment (ROI) analysis from a hospital perspective was conducted using a decision tree model (TDM versus AUC-based dosing) to simulate treatment cost (personnel, serum sampling and drug cost), vancomycin-associated AKI risk and cost up to 14 days.
Environ Geochem Health
January 2025
Department of Chemistry, Chulalongkorn University, Bangkok, Thailand.
The accumulation pattern of some inorganic pollutants in quarry sites around Ogun State was modeled using a Fuzzy comprehensive assessment (FCA). Potentially toxic elements (PTEs) and naturally occurring radionuclides materials (NORMs) were assessed from soil samples collected from ten quarry sites in three districts (Odeda, Ajebo, and Ijebu Ode) in Ogun State. Three (3) NORMs ( K, U, Th) were assessed using gamma spectrometer with a NaI detector while ten (10) PTEs (As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) were determined by digestion method using Inductively coupled plasma optical emission spectrophotometer.
View Article and Find Full Text PDFAnal Chem
January 2025
Mechanical Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
Total free thiols are an important marker of the whole-body redox state, which has been shown to be associated with clinical outcome in health and disease. Recent investigations have suggested that increased insight may be gained by monitoring alterations of redox state in response to exercise and hypoxia and to monitor redox trajectories in disease settings. However, conducting such studies is challenging due to the requirement for repeated venous blood sampling and intensive lab work.
View Article and Find Full Text PDFAnimal Model Exp Med
January 2025
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Background: In a previous study, we found that Atractylodes macrocephala and Paeoniae radix (AM-PR) was useful for the alleviation of functional constipation (FC). However, the precise mechanism underlying the compatibility between AM and PR in the treatment of FC remains uncertain. This study aims to analyze the pharmacokinetic differences in the active ingredients in the blood of rat models with FC when applied individually and in combination with AM-PR.
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