Reactions of Oxaprozin-1-0-Acyl Glucuronide in Solutions of Human Plasma and Albumin
Acyl glucuronides are major metabolites of many carboxylic acids including drugs, various chemicals, as well as endogenously formed compounds such as bilirubin and benzoic acid. Because of their susceptibility to nucleophilic attack acyl glucuronides are generally less stable than other glucuronides (1). Two reactions, hydrolysis and rearrangement (isomerization by acyl migration), contribute to this instability. Both reactions can occur at physiologic pH values. The extent to which they occur depends on the reactivity of the acyl glucuronide which in turn depends on the structure of its aglycone (2,3).
KeywordsHuman Serum Albumin Covalent Binding Decanoic Acid Human Albumin Acyl Migration
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- 4.R. Gugler, The effect of disease on the response to drugs, in “Proceedings of the 7th International Congress of Pharmacology”, P. Duchéne-Mairwaz, ed., Pergamon Press, Oxford (1979).Google Scholar
- 6.P.C. Smith, A.F. McDonagh, and L.Z. Benet, Covalent binding of zomepirac acyl glucuronide to albumin in healthy human volunteers, Hepatology 4: 1059 (1984).Google Scholar
- 12.A.J. Lewis, R.P. Carlson, J. Chang, S.C. Gilman, S. Nielson, M.E. Rosenthale, F.W. Janssen, and H.W. Ruelius, The pharmacological profile of oxaprozin, an antiinflammatory and analgesic agent with low gastrointestinal toxicity, Curr Ther Res 34: 777–794 (1983).Google Scholar
- 19.S-W.M. Koh and G.E. Means, Characterization of a small apolar anion binding site of human serum albumin, Arch Biochem Biophys 192: 73–79 (1979)Google Scholar
- 21.K.J. Fehske, W.E. Müller, U. Schlafer, and U. Wollert, Characterization of two important drug binding sites on human serum albumin, Prog Drug Protein Binding, Proc Lect Symp, 2nd 5–15 (1981)Google Scholar