Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 24, 1994 - Issue 6
25
Views
12
CrossRef citations to date
0
Altmetric
Research Article

Irreversible binding of tolmetin to macromolecules via its glucuronide: Binding to blood constituents, tissue homogenates and subcellular fractions in vitro

, &
Pages 495-506 | Received 01 Mar 1993, Published online: 22 Sep 2008
 

Abstract

1. The degradation of tolmetin glucuronide (TG) in biological fluids and tissue homogenates appears to follow first-order kinetics and is quite rapid in plasma. TG degradation was minimized upon the addition of phenylmethylsulphonyl fluoride (PMSF) and 1,4-saccharolactone, suggesting that the majority of the degradation may be enzymatic, rather than chemical hydrolysis.

2. Irreversible binding via TG was detected in all tissue preparations examined. Upon addition of an inhibitor of esterases (PMSF) to human serum albumin (HSA) and plasma, binding was extensive (2.5%) and the extent of binding was both time- and pH-dependent. Similar extents of binding were obtained with most tissue homogenates, except for spleen and intestine which exhibited much lower binding.

3. Incubation of TG with microsomal protein from sheep and rat yielded no significant differences. Incubations of tolmetin (T) and TG with microsomes, as well as tissue homogenates, indicates that irreversible binding occurs only in the presence of TG.

4. Irreversible binding occurred in all of the blood constituents, the highest extent with haemolyzed erythrocytes. The extent of binding was 15 times higher in disrupted versus intact red blood cells, suggesting a correlation between the extent of binding and the overall exposure of TG to the macromolecules to which it may bind irreversibly.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.