Species-related exposure of phase II metabolite gemfibrozil 1-O-β-glucuronide between human and mice: A net induction of mouse P450 activity was revealed

2017 ◽  
Vol 38 (9) ◽  
pp. 535-542 ◽  
Author(s):  
Min Luo ◽  
Manyun Dai ◽  
Hante Lin ◽  
Minzhu Xie ◽  
Jiao Lin ◽  
...  
Author(s):  
Gerard J. Stroomberg ◽  
Herman Zappey ◽  
Ruud J.C.A. Steen ◽  
Cornelis A.M. van Gestel ◽  
Freek Ariese ◽  
...  

2000 ◽  
Vol 48 (1) ◽  
pp. 45-47 ◽  
Author(s):  
Ehab A. ABOURASHED ◽  
Farouk S. EL-FERALY ◽  
Ikhlas A. KHAN ◽  
Charles D. HUFFORD
Keyword(s):  
Phase Ii ◽  

2014 ◽  
Vol 452 ◽  
pp. 25-30 ◽  
Author(s):  
Jens Martens-Lobenhoffer ◽  
Roman N. Rodionov ◽  
Stefanie M. Bode-Böger

2017 ◽  
Vol 40 (8) ◽  
pp. 972-979 ◽  
Author(s):  
Dong Wook Lee ◽  
Youra Kang ◽  
Mi Jeong Kang ◽  
Keumhan Noh ◽  
Ju Hyun Kim ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1576 ◽  
Author(s):  
Han Xing ◽  
Dexuan Kong ◽  
Chen Ning ◽  
Ying Kong ◽  
Chang Ren ◽  
...  

GL-V9 is a prominent derivative of wogonin with a wide therapeutic spectrum and potent anti-tumor activity. The metabolism characteristics of GL-V9 remain unclear. This study aimed to clarify the metabolic pathway of GL-V9 and investigate the generation of its glucuronidation metabolites in vitro and in vivo. HPLC-UV-TripleTOF was used to identify metabolites. The main metabolite that we found was chemically synthesized and the synthetic metabolite was utilized as standard substance for the subsequent metabolism studies of GL-V9, including enzyme kinetics in liver microsomes of five different species and reaction phenotyping metabolism using 12 recombinant human UDP-glucuronosyltransferase (UGT) isoforms. Results indicated that the glucuronidation reaction occurred at C5-OH group, and 5-O-glucuronide GL-V9 is the only glucuronide metabolite and major phase II metabolite of GL-V9. Among 12 recombinant human UGTs, rUGT1A9 showed the strongest catalytic capacity for the glucuronidation reaction of GL-V9. rUGT1A7 and rUGT1A8 were also involved in the glucuronidation metabolism. Km of rUGT1A7-1A9 was 3.25 ± 0.29, 13.92 ± 1.05, and 4.72 ± 0.28 μM, respectively. In conclusion, 5-O-glucuronide GL-V9 is the dominant phase II metabolite of GL-V9 in vivo and in vitro, whose formation rate and efficiency are closely related to isoform-specific metabolism profiles and the distribution of UGTs in different tissues of different species.


2007 ◽  
Vol 360 (2) ◽  
pp. 490-495 ◽  
Author(s):  
Yoshinori Ikenaka ◽  
Masumi Ishizaka ◽  
Heesoo Eun ◽  
Yuichi Miyabara

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