Can In Vitro Metabolism-Dependent Covalent Binding Data in Liver Microsomes Distinguish Hepatotoxic from Nonhepatotoxic Drugs? An Analysis of 18 Drugs with Consideration of Intrinsic Clearance and Daily Dose

2008 ◽  
Vol 21 (9) ◽  
pp. 1814-1822 ◽  
Author(s):  
R. Scott Obach ◽  
Amit S. Kalgutkar ◽  
John R. Soglia ◽  
Sabrina X. Zhao
Keyword(s):  
Covalent Binding ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
In Vitro Metabolism ◽  
Binding Data ◽  
Daily Dose

The in vitro metabolism and covalent binding of benzo[a]pyrene to dna catalysed by trout liver microsomes

1979 ◽  
Vol 25 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Jorma T. Ahokas ◽  
Hannu Saarni ◽  
Daniel W. Nebert ◽  
Olavi Pelkonen
Keyword(s):  
Covalent Binding ◽  
Liver Microsomes ◽  
In Vitro Metabolism

Can In Vitro Metabolism-Dependent Covalent Binding Data Distinguish Hepatotoxic from Nonhepatotoxic Drugs? An Analysis Using Human Hepatocytes and Liver S-9 Fraction

2009 ◽  
Vol 22 (2) ◽  
pp. 332-340 ◽  
Author(s):  
Jonathon N. Bauman ◽  
Joan M. Kelly ◽  
Sakambari Tripathy ◽  
Sabrina X. Zhao ◽  
Wing W. Lam ◽  
...  
Keyword(s):  
Covalent Binding ◽  
Human Hepatocytes ◽  
In Vitro Metabolism ◽  
Binding Data

P160 - In vitro metabolism of endosulfan sulfate in human liver microsomes, S9 fractions and hepatocytes

2020 ◽  
Vol 35 (1) ◽  
pp. S71-S72
Author(s):  
Hwa-Kyung Lee ◽  
Jeong-Han Kim ◽  
Tae Yeon Kong ◽  
Won-Gu Choi ◽  
Ju-Hyun Kim ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
In Vitro Metabolism ◽  
Endosulfan Sulfate

scholarly journals CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes

2007 ◽  
Vol 28 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Xiao-ping Zhao ◽  
Jiao Zhong ◽  
Xiao-quan Liu ◽  
Guang-ji Wang
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
In Vitro Metabolism

In vitro metabolism in Sprague–Dawley rat liver microsomes of forsythoside A in different compositions of Shuang–Huang–Lian

Fitoterapia ◽  
2011 ◽  
Vol 82 (8) ◽  
pp. 1222-1230 ◽  
Author(s):  
Wei Zhou ◽  
Liu-qing Di ◽  
Jin-jun Shan ◽  
Xiao-lin Bi ◽  
Le-tian Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Sprague Dawley Rat

In Vitro Metabolism of E2, G2: Novel Bile Acid-Coupling Camptothecin Analogues, in Rat Liver Microsomes

2021 ◽  
Vol 16 ◽  
Author(s):  
Xiangli Zhang ◽  
Qin Shen ◽  
Yi Wang ◽  
Leilei Zhou ◽  
Qi Weng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Phase I ◽  
Rat Liver ◽  
Deoxycholic Acid ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Rat Liver Microsomes ◽  
Camptothecin Analogues

Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues by introducing deoxycholic acid in 20-position of CPT(camptothecin) with greater anticancer activity and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase Ⅰ and Phase Ⅱ metabolism of E2 and G2 in rat liver microsomes were performed respectively, and the mixed incubation of phase I and phase Ⅱ metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic clearance of G2 was 174.7mL/min. mg protein, more than three times of that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).

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