Evaluation of preclinical safety profile of SPH3127, a direct renin inhibitor, after 28-day repeated oral administration in Sprague-Dawley rats and cynomolgus monkeys

2019 ◽  
Vol 109 ◽  
pp. 104484
Author(s):  
Yu Mao ◽  
Leduo zhang ◽  
Hua Li ◽  
Xin Li ◽  
Yanjun Liu ◽  
...  
NanoImpact ◽  
2020 ◽  
Vol 19 ◽  
pp. 100236
Author(s):  
Zhangjian Chen ◽  
Shuo Han ◽  
Di Zhou ◽  
Pai Zheng ◽  
Shupei Zhou ◽  
...  

Xenobiotica ◽  
2012 ◽  
Vol 43 (2) ◽  
pp. 169-181 ◽  
Author(s):  
James M. Mathews ◽  
Sherri S. Brown ◽  
Purvi R. Patel ◽  
Sherry R. Black ◽  
Troy T. Banks ◽  
...  

2005 ◽  
Vol 33 (11) ◽  
pp. 1688-1699 ◽  
Author(s):  
Christopher L. Shaffer ◽  
Mithat Gunduz ◽  
Thomas N. O'Connell ◽  
R. Scott Obach ◽  
Shiyin Yee

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.


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