Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Regular Articles
Glucuronidation of 2-(4-Chlorophenyl)-5-(2-Furyl)-4-Oxazoleacetic Acid (TA-1801A) in Humans: Species Differences in Liver and Intestinal Microsomes
Hidefumi KAJIToshiyuki KUME
Author information
JOURNAL FREE ACCESS

2005 Volume 20 Issue 3 Pages 206-211

Details
Abstract

  The metabolism of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-4-oxazoleacetate (TA-1801), a potent hypolipidemic agent, was studied in humans after oral administration and compared with that found in rats, rabbits, and dogs previously. Hydrolysis of the ethyl ester to produce metabolite M1 (TA-1801 active form; TA-1801A) is the first metabolic step and the subsequent biotransformation includes the glucuronidation to form the metabolite M4 and the oxidation to form the metabolites M2 and M3. The metabolism of TA-1801 in humans was qualitatively similar to that in the experimental animals studied, although species differences were seen in the amount of metabolites. M4, the glucuronide of TA-1801A was the most abundant metabolite in human urine (24.3% of the dose). In vitro studies using human liver and jejunum microsomes indicated that the TA-1801A glucuronosyltransferase activity in human jejunum microsomes was 2-fold higher than that in liver microsomes. With regard to the interspecies differences in the TA-1801A glucuronosyltransferase activities, the intrinsic clearance for the TA-1801A glucuronidation in liver microsomes was in the following order: rabbit>monkey>human=rat=dog. In jejunum microsomes, the intrinsic clearance for the TA-1801A glucuronidation was in the following order: human>monkey>rabbit>rat=dog. These results suggest that the species differences in the intestinal TA-1801A glucuronidation contribute to the species differences in the excretion rate of TA-1801A glucuronide into the urine.

Content from these authors

This article cannot obtain the latest cited-by information.

© 2005 by The Japanese Society for the Study of Xenobiotics
Previous article Next article
feedback
Top