[ Pharmaceutical Sciences Asia - ONLINE ]
Print ISSN 2586-8195 E-ISSN 2586-8470
[ Journal Abbreviation: Pharm.Sci.Asia ]
Mahidol University Journal of Pharmaceutical Sciences
  FORMER NAME   "Mahidol University Journal of Pharmaceutical Sciences" Published Since 1974

 
Abstracts

Pharm Sci Asia ; 35(1),
 

Gemfibrozil Glucuronidation in Human Liver Microsomes is Catalyzed by UDP-Glucuronosyltransferase 2B7

V. Uchaipichat,* P.I. Mackenzie and J.O. Miners

-


This study aimed to characterize the glucuronidation kinetics of gemfibrozil (GBZ) by human liver microsomes (HLMs) and to identify the human UDP-glucuronosyltransferase (UGT) enzymes responsible for these reactions. Using HLMs, the 2-Michaelis Menten kinetics were observed for GBZ glucuronidation with the mean high- and low-affinity apparent Km values of 5.6 ? 2.1 ?M (Vmax 444 ? 176 pmol/min.mg) and 316 ? 113 ?M (Vmax 1909 ? 838 pmol/min.mg), respectively. In addition, GBZ glucuronidation by HLMs was well described by a two-site model with mean derived binding affinity (Ks) and Vmax were 9.2 ? 3.2 ?M and 889 ? 437 pmol/min.mg, respectively. GBZ glucuronidation by UGT 1A3 (Km 386 ? 2 ?M) and 1A9 (Km 47 ? 0.3 ?M) exhibited Michaelis-Menten kinetics, whereas substrate inhibition (Km 378 ? 25 ?M and Ksi 2891 ? 319 ?M) was observed with UGT1A6. Similar to HLMs, GBZ glucuronidation by UGT2B7 was well described by the two-site kinetic model which provided a Ks value of 7.0 ? 0.9 ?M. Comparison of kinetic data suggests that UGT2B7 appears to be the enzyme responsible for the high-affinity component of human liver microsomal GBZ glucuronidation. These conclusions were confirmed using UGT2B7 (fluconazole) selective inhibitors.


Keyword:

COPD, drug counseling, pharmacy, Gemfibrozil, UDP-Glucuronosyltransferase, GBZ, human liver microsomes




Download full paper (PDF File size: 156.92 KB.)





Vol.35
No.1-4
2008

See other volume

 
 
 

Home
Aims and Scope
Editorial Board
Publication Ethics
Instruction to Authors
Announcement
All Volumes & Issues
Submit Online
Contact us
   
Search
   
Faculty of Pharmacy Mahidol University
Mahidol University
Member's menu

You're now loging on with following account:
Guest (unknown)

Please Sign in or Register



    Copyright © 2017
    Faculty of Pharmacy, Mahidol University, THAILAND