Studies on pharmacokinetics, body distribution, plasma protein binding rate, and excretion of 1-methyl hydantoin in rats in vivo

2017 ◽  
Vol 40 (2) ◽  
pp. 102-110
Author(s):  
Shihan Wang ◽  
Xiangqun Jin ◽  
Yang Xu ◽  
Xinyu Hu ◽  
Zuying Lv ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yuxiao Xia ◽  
Li Zhang ◽  
Yanhong Zhao ◽  
Xiangdong Liu ◽  
Liang Cai ◽  
...  

Objective. This work evaluated the potential of 68Ga-labelledNOTA-ICG (1,4,7-triazacyclononane-1,4,7-triacetic acid indocyanine green) for liver reserve imaging. Methods. To determine the optimal conditions for generating 68Ga-NOTA-ICG, various reaction parameters were implemented. Quality control analysis was performed using different chromatography techniques. The in vitro and in vivo stability was also measured at specific time points. The radioactivity ratio between n-octanol and water was determined to evaluate the water solubility of 68Ga-NOTA-ICG. The plasma-protein binding rate of the labelled compound was determined by the methanol method. The biodistribution and imaging findings were evaluated in normal animals at different time points after injection. A preliminary imaging evaluation was performed using an animal model of hepatic ischaemia-reperfusion injury, which was confirmed by pathology. Results. 68Ga-NOTA-ICG was prepared with very high radiochemical purity (>98%) by reacting at 90°C for 10 min at pH = 3.5∼4.0, with excellent stability in vivo and in vitro (>95% 3 h postpreparation). The in vitro plasma-protein binding rate of 68Ga-NOTA-ICG was 13.01 ± 0.7%, and it showed strong water solubility log P=−2.01±0.04. We found that in addition to excretion through the biliary tract and intestines, 68Ga-NOTA-ICG can be excreted through the urinary tract. The image quality of 68Ga-NOTA-ICG was very high; imaging agent retained in the area of liver injury could clearly be observed. Conclusion. This is the first report on a 68Ga-labelled NOTA-ICG fragment for liver reserve function studies. This complex has promise as a candidate agent for liver reserve imaging.


Author(s):  
Yilin Hou ◽  
Yuanyuan Zhao ◽  
Yu Li

Comparative molecular similarity index analysis (CoMSIA) was used to establish a three-dimensional quantitative structure–activity relationship (3D-QSAR) model with structural parameters of quinolones as the independent variables and plasma protein binding rate (logfb) as the dependent variable to predict the logfb values of remaining quinolones in this study. In addition, the mono-substituted and bis-substituted reaction schemes that significantly influenced the plasma protein binding rate of quinolones were determined through an analysis of the 3D-QSAR contour maps. It was found that the replacement of small groups, hydrophobic groups, electronegative groups, or hydrogen bond acceptor groups at the substitution sites significantly reduce the logfb values of quinolone derivatives. Furthermore, the mechanism of decrease in binding rate between trovafloxacin (TRO) derivatives and plasma protein was revealed qualitatively and quantitatively based on molecular docking and molecular dynamics simulation. After modification of the target molecule, 11 TRO derivatives with low plasma protein binding rates were screened (reduced by 0.50–24.18%). Compared with the target molecule, the molecular genotoxicity and photodegradability of the TRO derivatives was higher (genotoxicity increased by 4.89–21.36%, and photodegradability increased by 9.04–20.56%), and their bioconcentration was significantly lower (by 36.90–61.41%).


2006 ◽  
Vol 68 (4) ◽  
pp. 361-365 ◽  
Author(s):  
Takehiko KAKIZAKI ◽  
Yukiko YOKOYAMA ◽  
Masahiro NATSUHORI ◽  
Azusa KARASAWA ◽  
Satoshi KUBO ◽  
...  

1994 ◽  
Vol 17 (12) ◽  
pp. 1630-1634 ◽  
Author(s):  
Mikiro NAKASHIMA ◽  
Naoko TAKEUCHI ◽  
Motoko HAMADA ◽  
Kenji MATSUYAMA ◽  
Masataka ICHIKAWA ◽  
...  

2013 ◽  
Vol 19 (4) ◽  
pp. 721-727
Author(s):  
Haixin ZHANG ◽  
Kun HU ◽  
Jiming Ruan ◽  
Weidong ZHEN ◽  
Xianle YANG ◽  
...  

Chirality ◽  
1993 ◽  
Vol 5 (3) ◽  
pp. 120-125 ◽  
Author(s):  
Sascha Mayer ◽  
Ernst Mutschler ◽  
Hildegard Spahn-Langguth ◽  
Leslie Z. Benet

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