Abstract
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).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
E.M. Faed, Properties of acyl glucuronides: implications for studies of the pharmacokinetics and metabolism of acidic drugs, Drug Metab Rev 15: 1213–1249 (1984).
F.W. Janssen, S.K. Kirkman, C. Fenselau, M. Stogniew, B.R. Hofmann, E.M. Young, and H.W. Ruelius, Metabolic formation of N- and 0-glucuronides of 3-(p-chlorophenyl)thiazolo-[3,2-a] benzimidazole-2-acetic acid, Drug Metab Dispos 10: 599–604 (1982).
H.W. Ruelius, E.M. Young, S.K. Kirkman, R.T. Schillings, S.F. Sisenwine, and F.W. Janssen, Biological fate of acyl glucuronides in the rat, Biochem Pharmacol 34: 451–452 (1985).
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).
E.M. Faed and E.G. McQueen, Plasma half-life of clofibric acid in renal failure, Br J Clin Pharmacol 7: 407–410 (1979).
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).
A. Gautam, H. Seligson, E.R. Gordon, D. Seligson, and J.L. Boyer, Irreversible binding of conjugated bilirubin to albumin in cholestatic rats, J Clin Invest 73: 873–877 (1984).
A.F. McDonagh, L.A. Palma, J.J. Lauff, and T-W. Wu, Origin of mammalian biliprotein and rearrangement of bilirubin glucuronide in vivo in the rat, J Clin Invest 74: 763–770 (1984).
R.B. van Breemen and C. Fenselau, Acylation of albumin by 1–0-acyl glucuronides, Drug Metab Dispos 13: 318–320 (1985).
F.W. Janssen, W.J. Jusko, S.T. Chiang, S.K. Kirkman, P.J. Southgate, A.J. Coleman and H.W. Ruelius, Metabolism and kinetics of oxaprozin in normal subjects, Clin Pharmacol Ther 27: 352–362 (1980).
F.W. Janssen, S.K. Kirwan, J.A. Knowles, and H.W. Ruelius, Disposition of 4,5-diphenyl-2-oxazolepropionic acid (oxaprozin) in beagle dogs and rhesus monkeys, Drug Metab Dispos 6: 465–475 (1978).
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).
G.E. Means and M.L. Bender, Acetylation of human serum albumin by p-nitrophenyl acetate, Biochem 14: 4989–4994 (1975).
F.D. Boudinot, C.A. Homon, W.J. Jusko, and H.W. Ruelius, Protein binding of oxazepam and its glucuronide conjugates to human albumin, Biochem Pharmacol 34: 2115–2121 (1985).
N. Ohta, Y. Kurono, and K. Ikeda, Esterase-like activity of human serum albumin II:reaction with N-transcinnamoylimidazoles, J Pharm Sci 72: 385–388 (1983).
Y. Kurono, T. Kondo, and K. Ikeda, Esterase-like activity of human serum albumin III: enantioselectivity in the burst phase of reaction with p-nitrophenyl a-methoxyphenyl acetate, Arch Biochem Biophys 227: 339–341 (1983).
P.C. Smith, J. Hasegawa, P.N.J. Langendijk, and L.Z. Benet, Stability of acyl glucuronides in blood, plasma and urine: studies with zomepirac, Drug Metab Dispos 13: 110–112 (1985).
I. Sjöholm, B. Ekman, A. Kober, I. Ljungstedt-Pâhlman, B. Seiving, and T. Sjodin, Binding of drugs to human serum albumin. XI. The specificity of three binding sites as studied with albumin immobilized in microparticles, Mol Pharmacol 16: 767–777 (1979).
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)
N.P. Sollenne and G.E. Means, Characterization of a specific drug binding site of human serum albumin, Mol Pharmacol 15: 754–757 (1979)
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)
W.E. Müller and U. Wollert, Benzodiazepines: specific competitors for the binding of L-tryptophan to human serum albumin, Naunyn-Schmiedeberg’s Arch Pharmacol 288: 17–27 (1975).
K.J. Fehske, W.E. Müller, and U. Wollert, A highly reactive tyrosine residue as part of the indole and benzodiazepine binding site of human serum albumin, Biochem Biophys Acta 577: 346–359 (1979).
G.E. Means and H.L. Wu, The reactive tyrosine residue of human serum albumin: characterization of its reaction with diisopropylfluorophosphate, Arch Biochem Biophys 194: 526–530 (1979).
K.J. Fehske, W.E. Müller, and U. Wollert, Direct demonstration of the highly reactive tyrosine residue of human serum albumin located in fragment 299–585, Arch Biochem Biophys 205: 217–221 (1980)
B.J. Rowe and P.J. Meffin, Diisopropylfluorophosphate increases clofibric acid clearance: supporting evidence for a futile cycle, J Pharmacol Exp Ther 230: 237–241 (1984).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Ruelius, H.W., Kirkman, S.K., Young, E.M., Janssen, F.W. (1986). Reactions of Oxaprozin-1-0-Acyl Glucuronide in Solutions of Human Plasma and Albumin. In: Kocsis, J.J., Jollow, D.J., Witmer, C.M., Nelson, J.O., Snyder, R. (eds) Biological Reactive Intermediates III. Advances in Experimental Medicine and Biology, vol 197. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5134-4_42
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5134-4_42
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5136-8
Online ISBN: 978-1-4684-5134-4
eBook Packages: Springer Book Archive