Regio- and Stereospecific N-Glucuronidation of Medetomidine: The Differences between UDP Glucuronosyltransferase (UGT) 1A4 and UGT2B10 Account for the Complex Kinetics of Human Liver Microsomes

2008 ◽  
Vol 36 (8) ◽  
pp. 1529-1537 ◽  
Author(s):  
Sanna Kaivosaari ◽  
Päivi Toivonen ◽  
Olli Aitio ◽  
Julius Sipilä ◽  
Mikko Koskinen ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Kinetics Of

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

UDP-glucuronosyltransferase activities in human liver microsomes and in some laboratory animal species

1981 ◽  
Vol 30 (17) ◽  
pp. 2507-2510 ◽  
Author(s):  
Jean A. Boutin ◽  
Alain Jacquier ◽  
Anne-Marie Batt ◽  
Philippe Marlière ◽  
Gérard Siest
Keyword(s):  
Human Liver ◽  
Laboratory Animal ◽  
Animal Species ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase

scholarly journals Kinetics of Trihalogenated Acetic Acid Metabolism and Isoform Specificity in Liver Microsomes

2011 ◽  
Vol 30 (5) ◽  
pp. 551-561 ◽  
Author(s):  
Shakil A. Saghir ◽  
Burhan I. Ghanayem ◽  
Irvin R. Schultz
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Water Disinfection ◽  
Metabolic Clearance ◽  
Interspecies Differences ◽  
P450 Reductase ◽  
Cyp 2E1 ◽  
Chemical Inhibitors ◽  
Kinetics Of

This study determined the metabolism of 3 drinking water disinfection by-products (halogenated acetic acids [HAAs]), bromodichloroacetic acid (BDCAA), chlorodibromoacetic acid (CDBAA), and tribromoacetic acid (TBAA), using rat, mouse, human liver microsomes, and recombinant P450. Metabolism proceeded by reductive debromination forming a di-HAA; the highest under nitrogen >>2% oxygen > atmospheric headspaces. Vmax for the loss of tri-HAA was 4 to 5 times higher under nitrogen than atmospheric headspace. Intrinsic metabolic clearance was TBAA>CDBAA>>BDCAA. At the high substrate concentrations, tri-HAA consumption rate was 2 to 3 times higher than the formation of di-HAA. Liberation of Br− from TBAA corresponded to the expected amount produced after DBAA formation, indicating retention of Br− by additional metabolite/metabolites. Subsequent experiments with CDBAA detected negligible formation of chlorodibromomethane (CDBM) and failed to account for the missing tri-HAA. Carbon monoxide and especially diphenyleneiodonium ([DPI] P450 reductase inhibitor) blocked CDBAA metabolism. Other chemical inhibitors were only partially able to block CDBAA metabolism. Most effective were inhibitors of CYP 2E1 and CYP 3A4. Immunoinhibition studies using human liver microsomes and anti-human CYP 2E1 antibodies were successful in reducing CDBAA metabolism. However, CDBAA metabolism in wild-type (WT) and CYP 2E1 knockout (KO) mouse liver microsomes was similar, suggesting significant interspecies differences in CYP isoform in tri-HAA metabolism. Additional assessment of CYP isoform involvement was complicated by the finding that recombinantly expressed rat and human P450 reductase was able to metabolize CDBAA, which may be a contributing factor in interspecies differences in tri-HAA metabolism.

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