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1.
Pharmaceutics ; 13(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799884

RESUMO

Supinoxin is a novel anticancer drug candidate targeting the Y593 phospho-p68 RNA helicase, by exhibiting antiproliferative activity and/or suppression of tumor growth. This study aimed to characterize the in vitro and in vivo pharmacokinetics of supinoxin and attempt physiologically based pharmacokinetic (PBPK) modeling in rats. Supinoxin has good permeability, comparable to that of metoprolol (high permeability compound) in Caco-2 cells, with negligible net absorptive or secretory transport observed. After an intravenous injection at a dose range of 0.5-5 mg/kg, the terminal half-life (i.e., 2.54-2.80 h), systemic clearance (i.e., 691-865 mL/h/kg), and steady state volume of distribution (i.e., 2040-3500 mL/kg) of supinoxin remained unchanged, suggesting dose-independent (i.e., dose-proportional) pharmacokinetics for the dose ranges studied. After oral administration, supinoxin showed modest absorption with an absolute oral bioavailability of 56.9-57.4%. The fecal recovery following intravenous and oral administration was 16.5% and 46.8%, respectively, whereas the urinary recoveries in both administration routes were negligible. Supinoxin was mainly eliminated via NADPH-dependent phase I metabolism (i.e., 58.5% of total clearance), while UDPGA-dependent phase II metabolism appeared negligible in the rat liver microsome. Supinoxin was most abundantly distributed in the adipose tissue, gut, and liver among the nine major tissues studied (i.e., the brain, liver, kidneys, heart, lungs, spleen, gut, muscles, and adipose tissue), and the tissue exposure profiles of supinoxin were well predicted with physiologically based pharmacokinetics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-18002072

RESUMO

GVF algorithm has been studied actively and it will be able to apply to quite many applications. This paper presents GVF algorithm for the segmentation of a sequence of images. Traditional GVF algorithm can extract contour of object in an image. However, in the video sequence images or CT images traditional GVF algorithm had some problems. We can treat these problems under motion tracking using Motion Estimation using Mean Square Error (MSE). Initial point problem is very important in GVF algorithm. We applied extracted initial point of first image to the second image. In other word, previous initial contour can be used to the next initial contour.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Movimento (Física) , Tomografia Computadorizada por Raios X , Humanos
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