Stereoselective hepatic disposition of a diastereomeric pair of αvβ3antagonists in rat

Xenobiotica ◽  
2003 ◽  
Vol 33 (11) ◽  
pp. 1125-1137 ◽  
Author(s):  
T. Prueksaritanont ◽  
X. Xu ◽  
P. Deluna ◽  
M. Yamazaki ◽  
J. H. Lin
2000 ◽  
Vol 1 (2) ◽  
pp. 163-180 ◽  
Author(s):  
B. Sallustio ◽  
L. Sabordo ◽  
A. Evans ◽  
R. Nation

1991 ◽  
Vol 39 (3) ◽  
pp. 761-764 ◽  
Author(s):  
Yusuke TANIGAWARA ◽  
Yan-Ling HE ◽  
Katsuhiko OKUMURA ◽  
Ryohei HORI
Keyword(s):  

2011 ◽  
Vol 300 (1) ◽  
pp. G130-G136 ◽  
Author(s):  
Michael S. Roberts ◽  
Xin Liu ◽  
Yuhong Zou ◽  
Gerhard A. Siebert ◽  
Ping Chang ◽  
...  

It has been reported that the adjuvant-induced inflammation could affect drug metabolism in liver. Here we further investigated the effect of inflammation on drug transport in liver using taurocholate as a model drug. The hepatic disposition kinetics of [3H]taurocholate in perfused normal and adjuvant-treated rat livers were investigated by the multiple indicator dilution technique and data were analyzed by a previously reported hepatobiliary taurocholate transport model. Real-time RT-PCR was also performed to determine the mRNA expression of liver bile salt transporters in normal and diseased livers. The uptake and biliary excretion of taurocholate were impaired in the adjuvant-treated rats as shown by decreased influx rate constant kin (0.65 ± 0.09 vs. 2.12 ± 0.30) and elimination rate constant kbe (0.09 ± 0.02 vs. 0.17 ± 0.04) compared with control rat group, whereas the efflux rate constant kout was greatly increased (0.07 ± 0.02 vs. 0.02 ± 0.01). The changes of mRNA expression of liver bile salt transporters were found in adjuvant-treated rats. Hepatic taurocholate extraction ratio in adjuvant-treated rats (0.86 ± 0.05, n = 6) was significantly reduced compared with 0.93 ± 0.05 ( n = 6) in normal rats. Hepatic extraction was well correlated with altered hepatic ATP content ( r2 = 0.90). In conclusion, systemic inflammation greatly affects hepatic ATP content/production and associated transporter activities and causes an impairment of transporter-mediated solute trafficking and pharmacokinetics.


1994 ◽  
Vol 23 (5) ◽  
pp. 949-952 ◽  
Author(s):  
Masaaki Kojima ◽  
Kiyohiko Nakajima ◽  
Masanobu Tsuchimoto ◽  
Miki Tanaka ◽  
Tetsuya Suzuta ◽  
...  

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ming Zhong ◽  
Xiaoting Tian ◽  
Shuoji Chen ◽  
Mingcang Chen ◽  
Ziqiong Guo ◽  
...  

Abstract Background Modern pharmacological studies have demonstrated that Baihe–Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds. Methods In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing. Results Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression. Conclusions This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.


2019 ◽  
Vol 58 (19) ◽  
pp. 12538-12541 ◽  
Author(s):  
Sudip Kumar Bera ◽  
Arijit Singha Hazari ◽  
Goutam Kumar Lahiri
Keyword(s):  

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