In Vitro Inhibitory Effect of 1-Aminobenzotriazole on Drug Oxidations in Human Liver Microsomes: a Comparison with SKF-525A

2005 ◽  
Vol 20 (5) ◽  
pp. 351-357 ◽  
Author(s):  
Chie Emoto ◽  
Shigeo Murase ◽  
Yasufusa Sawada ◽  
Kazuhide Iwasaki
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Human Liver Microsomes

scholarly journals In-vitro assessment of CYP3A4 and CYPC29 inhibition potential of Lupeol using human liver microsomes

2019 ◽  
Vol 9 (2) ◽  
pp. 231-236
Author(s):  
LAXMAN DATTU KHATAL ◽  
Harinath More
Keyword(s):  
Drug Interactions ◽  
Human Liver ◽  
Biological Activities ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Human Liver Microsomes ◽  
Metabolite Formation ◽  
Physiological Concentration

Background: Lupeol is a dietary triterpene, possesses numerous biological activities. Lupeol is currently under development for chemotherapy and chemoprevention. The aim of present study was to determine the potential inhibitory effect of Lupeol on cytochrome P450 (CYP3A4 and CYP2C9 isozymes) activities in human liver microsomes (HLM). Methods:  The inhibition studies were conducted using testosterone 6β-hydroxylase (CYP3A4), and diclofenac 4’-Hydroxylase (CYP2C9) activity assay using positive control Ketoconazole and Sulphaphenazole, respectively. Inhibition study was performed by incubating lupeol (0 to 20 μM) with human liver microsomes, and the metabolite formation was analyzed by liquid chromatography-Tandem Mass Spectrometry (LC-MS/MS). Results: Luepol did not inhibit CYP3A4 and CYP2C9 isozymes mediated activities in human liver microsomes up to a maximum tested concentration of 20µM based on solubility under tested invitro conditions. Conclusions: Lupeol is not an inhibitor of the CYP3A4 and CYP2C9 isozymes. IC50 is greater than highest tested concentration as well as physiological concentration, where effect was measured with confidence. Therefore, clinically relevant pharmacokinetic herb-drug interactions are unlikely to occur between Lupeol and co-administered substrates of these CYP isozymes. Looking at the spectrum of biological activities and CYP inhibition potential of Lupeol; Lupeol can be used as adjuvant/ chemotherapy agent/ chemopreventive agent in therapy. Keywords: Lupeol, HLM, CYP3A4 and CYP2C9, Inhibition, herb–drug interactions

scholarly journals Metabolic Interaction of the Active Constituents ofCoptis chinensisin Human Liver Microsomes

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Songcan Liu ◽  
Xinfeng Zhang ◽  
Furong Qiu ◽  
Ping Miao ◽  
Shujiao Shen ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Human Liver ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Human Liver Microsomes ◽  
Coptis Chinensis ◽  
Active Constituents ◽  
Metabolic Interaction ◽  
Inhibition Experiment

Coptis chinensisis commonly used in traditional Chinese medicine. The study investigated metabolic interaction of the active constituents (berberine, coptisine, palmatine, and jatrorrhizine) ofCoptis chinensisin human liver microsomes. After incubation of the four constituents ofCoptis chinensisin HLMs, the metabolism of the four constituents was observed by HPLC. Thein vitroinhibition experiment between the active constituents was conducted, and IC50value was estimated. Coptisine exhibited inhibitions against the formation of the two metabolites of berberine with IC50values of 6.5 and 8.3 μM, respectively. Palmatine and jatrorrhizine showed the weaker inhibitory effect on the formation of the metabolites of berberine. Berberine showed a weak inhibitory effect on the production of coptisine metabolite with an IC50value of 115 μM, and palmatine and jatrorrhizine had little inhibitory effect on the formation of coptisine metabolite. Berberine, coptisine, and jatrorrhizine showed no inhibitory effect on the generation of palmatine metabolite (IC50> 200 μM). The findings suggested that there are different degrees of metabolic interaction between the four components. Coptisine showed the strongest inhibition toward berberine metabolism.

scholarly journals Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors β and γ, DN203368

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 776
Author(s):  
Sin-Eun Kim ◽  
Seung-Bae Ji ◽  
Euihyeon Kim ◽  
Minseon Jeong ◽  
Jina Kim ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Human Liver ◽  
High Resolution Mass Spectrometry ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Rat Liver Microsomes ◽  
High Resolution Mass ◽  
Resolution Mass

DN203368 ((E)-3-[1-(4-[4-isopropylpiperazine-1-yl]phenyl) 3-methyl-2-phenylbut-1-en-1-yl] phenol) is a 4-hydroxy tamoxifen analog that is a dual inverse agonist of estrogen-related receptor β/γ (ERRβ/γ). ERRγ is an orphan nuclear receptor that plays an important role in development and homeostasis and holds potential as a novel therapeutic target in metabolic diseases such as diabetes mellitus, obesity, and cancer. ERRβ is also one of the orphan nuclear receptors critical for many biological processes, such as development. We investigated the in vitro metabolism of DN203368 by conventional and metabolomic approaches using high-resolution mass spectrometry. The compound (100 μM) was incubated with rat and human liver microsomes in the presence of NADPH. In the metabolomic approach, the m/z value and retention time information obtained from the sample and heat-inactivated control group were statistically evaluated using principal component analysis and orthogonal partial least-squares discriminant analysis. Significant features responsible for group separation were then identified using tandem mass spectra. Seven metabolites of DN203368 were identified in rat liver microsomes and the metabolic pathways include hydroxylation (M1-3), N-oxidation (M4), N-deisopropylation (M5), N,N-dealkylation (M6), and oxidation and dehydrogenation (M7). Only five metabolites (M2, M3, and M5-M7) were detected in human liver microsomes. In the conventional approach using extracted ion monitoring for values of mass increase or decrease by known metabolic reactions, only five metabolites (M1-M5) were found in rat liver microsomes, whereas three metabolites (M2, M3, and M5) were found in human liver microsomes. This study revealed that nontargeted metabolomics combined with high-resolution mass spectrometry and multivariate analysis could be a more efficient tool for drug metabolite identification than the conventional approach. These results might also be useful for understanding the pharmacokinetics and metabolism of DN203368 in animals and humans.

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

Investigations on the metabolic pathways of cyclosporine: II. Elucidation of the metabolic pathways in vitro by human liver microsomes

Xenobiotica ◽  
1991 ◽  
Vol 21 (9) ◽  
pp. 1199-1210 ◽  
Author(s):  
U. Christians ◽  
S. Strohmeyer ◽  
R. Kownatzki ◽  
H.-M. Schiebel ◽  
J. Bleck ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

Effect of Age on in Vitro Triazolam Biotransformation in Male Human Liver Microsomes

2003 ◽  
Vol 308 (3) ◽  
pp. 874-879 ◽  
Author(s):  
Kiran C. Patki ◽  
Lisa L. von Moltke ◽  
Jerold S. Harmatz ◽  
Leah M. Hesse ◽  
Michael H. Court ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Effect Of Age
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