Investigation into UDP-Glucuronosyltransferase (UGT) Enzyme Kinetics of Imidazole- and Triazole-Containing Antifungal Drugs in Human Liver Microsomes and Recombinant UGT Enzymes

2010 ◽  
Vol 38 (6) ◽  
pp. 923-929 ◽  
Author(s):  
Karine Bourcier ◽  
Ruth Hyland ◽  
Sarah Kempshall ◽  
Russell Jones ◽  
Jacqueline Maximilien ◽  
...  
Keyword(s):  
Enzyme Kinetics ◽  
Human Liver ◽  
Liver Microsomes ◽  
Antifungal Drugs ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Kinetics Of

Metabolic Characteristics of SM-1, a Novel PAC-1 Derivative, in Human Liver Microsomes

2021 ◽  
Vol 17 ◽  
Author(s):  
Ya Gong ◽  
Peiqi Wang ◽  
Jianming Li ◽  
Jinsong Ding
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Enzyme Kinetics ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Spectrometry Method ◽  
Mass Spectrometry Method ◽  
Metabolic Characteristics ◽  
Kinetics Of

Background and Objectives: SM-1 is a new synthetic small molecule compound with antitumor activity. The metabolism of SM-1 is a key parameter that needs to be evaluated to provide further insight into drug safety and efficacy in the early phases of drug development. Methods and Results: In this study, the biotransformation process of SM-1 including the metabolic pathways and major metabolites was investigated based on a liquid chromatography-mass spectrometry method. Upon incubation of SM-1 with human liver microsomes, five metabolites were identified, namely dihydrodiol formation (R1), hydroxylation (R2, R3 and R5), and debenzylation (R4) of SM-1, with R1 and R4 being the major metabolites. The enzyme kinetic parameters of SM-1 were determined by a liquid chromatography tandem mass spectrometry method. The enzyme kinetics of SM-1 obeyed the Michaelis-Menten equation. The Vmax, Km, and CLint of SM-1 in HLMs were 14.5 nmol/mg protein/h, 6.32 μM, and 2.29 mL/mg protein/h, respectively. The chemical inhibition studies showed that CYP450 isoenzymes were responsible for SM-1 metabolism in HLMs and CYP3A4 was the major CYP450 isoenzyme involved in the metabolism of SM-1; these findings were confirmed by using the human recombinant CYP3A4. Conclusions : Through identification of the biotransformation pathways and enzyme kinetics of SM-1, the metabolic enzymes for SM-1 in HLMs are characterized.

Effect of Commonly Used Organic Solvents on the Kinetics of Cytochrome P450 2B6- and 2C8-Dependent Activity in Human Liver Microsomes

2007 ◽  
Vol 35 (11) ◽  
pp. 1990-1995 ◽  
Author(s):  
Ragini Vuppugalla ◽  
Shu-Ying Chang ◽  
Hongjian Zhang ◽  
Punit H. Marathe ◽  
David A. Rodrigues
Keyword(s):  
Cytochrome P450 ◽  
Organic Solvents ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2B6 ◽  
Dependent Activity ◽  
Kinetics Of

scholarly journals Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Young Ji ◽  
Kwang Hyeon Liu ◽  
Ji Hyeon Jeong ◽  
Dae-Young Lee ◽  
Hyun Joo Shim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Index Value ◽  
Tuber Extract ◽  
Corydalis Tuber

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol1′-hydroxylation, with aKivalue of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate thein vivoextent of the observedin vitrointeractions.

scholarly journals Kinetics of tris (1-chloro-2-propyl) phosphate (TCIPP) metabolism in human liver microsomes and serum

Chemosphere ◽  
2016 ◽  
Vol 144 ◽  
pp. 1299-1305 ◽  
Author(s):  
Nele Van den Eede ◽  
Gregg Tomy ◽  
Fang Tao ◽  
Thor Halldorson ◽  
Stuart Harrad ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Kinetics Of
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