The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery

2010 ◽  
Vol 9 (12) ◽  
pp. 929-939 ◽  
Author(s):  
Dennis A. Smith ◽  
Li Di ◽  
Edward H. Kerns
Keyword(s):  
Drug Discovery ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
In Vivo Efficacy

scholarly journals Gallium-68-Labelled Indocyanine Green as a Potential Liver Reserve Imaging Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yuxiao Xia ◽  
Li Zhang ◽  
Yanhong Zhao ◽  
Xiangdong Liu ◽  
Liang Cai ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Water Solubility ◽  
Time Points ◽  
Binding Rate ◽  
Very High

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.

scholarly journals Probenecid: Its Chromatographic Determination, Plasma Protein Binding, and in vivo Pharmacokinetics in Dogs

2006 ◽  
Vol 68 (4) ◽  
pp. 361-365 ◽  
Author(s):  
Takehiko KAKIZAKI ◽  
Yukiko YOKOYAMA ◽  
Masahiro NATSUHORI ◽  
Azusa KARASAWA ◽  
Satoshi KUBO ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Chromatographic Determination ◽  
In Vivo Pharmacokinetics

scholarly journals In Vivo Microdialysis for Pharmacokinetic Investigations: A Plasma Protein Binding Study of Valproate in Rabbits.

1994 ◽  
Vol 17 (12) ◽  
pp. 1630-1634 ◽  
Author(s):  
Mikiro NAKASHIMA ◽  
Naoko TAKEUCHI ◽  
Motoko HAMADA ◽  
Kenji MATSUYAMA ◽  
Masataka ICHIKAWA ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
In Vivo Microdialysis ◽  
Binding Study

In vitro and in vivo irreversible plasma protein binding of beclobric acid enantiomers

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

The Role of Plasma Protein Binding in Drug Discovery

2007 ◽  
pp. 119-141 ◽  
Author(s):  
Roger E. Fessey ◽  
Rupert P. Austin ◽  
Patrick Barton ◽  
Andrew M. Davis ◽  
Mark C. Wenlock
Keyword(s):  
Drug Discovery ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein
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