The Metabolism of Ibuprofen by the Rat Liver
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Authors
Crimmins, Curtis A.
Issue Date
1984
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
In situ rat liver perfusion techniques were used to
examine the metabolism of ibuprofen by the rat liver.
Ibuprofen is a non-steroidal anti-inflammatory agent that is
clinically administered as a racemic mixture. It. is
metabolized by the oxidation of the isobutyl side chain and
by the chiral inversion of the methinyl carbon of the
propionic acid group. Results indicated that the inversion
is stereoselective, proceeding from R to S configuration and
not vice versa.
In this study, normal healthy livers were compared to
fatty diseased livers that had undergone diet-induced
cirrhosis. Results showed that the total hepatic clearance
of the R isomer was higher in the control livers than in the
fatty livers. However, this decrease in R clearance between
the control and fatty livers was not seen as a reduction of
the clearance due to inversion, but as a reduction in the
clearance due to mechanisms other than chiral inversion.
Thus, although a decrease in the ability to metabolize
ibuprofen was observed in the fatty livers, the chiral
inversion pathway was apparently unaffected
by liver disease.
This is a significant finding, since the
pharmacological activity of ibuprofen has been found to lie
almost exclusively in the S isomer. A reduction of the
ability to catalyze the R to the S isomer would greatly
diminish the drug's potency. Since ibuprofen is administered as a racemic mixture,
the chiral inversion pathway is very important to the metabolism of the drug.
Description
v, 39 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.