Reactions of oxaprozin-1-O-acyl glucuronide in solutions of human plasma and albumin

Advances in Experimental Medicine and Biology
H W RueliusF W Janssen

Abstract

Hydrolysis and rearrangement (isomerization by acyl migration) of oxaprozin glucuronide are greatly accelerated by plasma and human serum albumin. Albumin accounts for all the hydrolytic activity in plasma and no esterase is involved. The isomeric esters formed by rearrangement are also good substrates for the hydrolysis reaction. Another reaction between oxaprozin glucuronide and albumin leads to covalent binding of the aglycone. Similar reactions leading to covalent binding have been described for other acyl glucuronides by several investigators. In the case of oxaprozin, there is little or no potential for biological significance of covalent binding because the reaction is almost entirely inhibited by low concentrations of the drug. All three reactions are pH dependent but not to the same extent. They can be considered to be transacylations to the hydroxyl ion (hydrolysis), to a different OH-group of the glucuronic acid moiety (rearrangement) or to a nucleophilic group on the albumin molecule (covalent binding). All three reactions are greatly inhibited by the same compounds suggesting a common reaction site. This site has certain features in common with the indole or benzodiazepine binding site of human serum albumin. A sch...Continue Reading

Citations

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