Reactions of Oxaprozin-1-0-Acyl Glucuronide in Solutions of Human Plasma and Albumin

Ruelius, Hans W.; Kirkman, Sandra K.; Young, Emily M.; Janssen, F.J.J.G.

doi:10.1007/978-1-4684-5134-4_42

Cited by 47 publications

(26 citation statements)

References 13 publications

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“…1,2 These reactions are considered to proceed through transacylations to the hydroxyl ion, to a different OH-group of the glucuronic acid moiety and to a nucleophilic group on the protein molecule, respectively, as suggested in an oxaprozin glucuronide study. 3 Formation of irreversible binding of carboxylic acidcontaining drugs, such as nonsteroidal antiinflammatory drugs (NSAIDs), via their acyl glucuronide metabolites, is now well recognized and is a potential cause of hypersensitivity. 2,4,5 The exact mechanism underlying irreversible binding to proteins, however, has not yet been clarified due to the instability of acyl glucuronides.…”

mentioning

confidence: 99%

In Vitro Regioselective Stability of β‐1‐O‐ and 2‐O‐Acyl Glucuronides of Naproxen and Their Covalent Binding to Human Serum Albumin

Iwaki¹,

Ogiso²,

Inagawa³

et al. 1999

Journal of Pharmaceutical Sciences

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beta-1-O- (NAG) and 2-O-glucuronides (2-isomer) of (S)-naproxen (NA) were prepared to determine which positional isomer(s) of the acyl glucuronide of NA is responsible for forming covalent adducts with human serum albumin (HSA). Their comparative stability and covalent binding adduct formation with HSA were investigated at pH 7.4 and at 37 degreesC. NA and its acyl glucuronides were simultaneously determined by HPLC. Three positional isomers were formed successively after incubation of NAG in the buffer only. However, when NAG was incubated with HSA (30 mg/mL), isomers other than the 2-isomer were formed in little or negligible quantities. In HSA solution, NAG (kd = 2.08 +/- 0.08 h-1) was four times less stable than 2-isomer (kd = 0.51 +/- 0.02 h-1). NAG was degraded by hydrolysis (khyd = 1.01 +/- 0.10 h-1) and isomerization (kiso = 1.07 +/- 0.07 h-1) to the same extent; however, hydrolysis was predominant for the 2-isomer (kd = 0.51 +/- 0.02 h-1). The incubation of both NAG and 2-isomer with HSA led to the formation of a covalent adduct; however, the adduct formation from the 2-isomer proceeded more slowly than that from NAG. The present results suggest that the covalent binding of NA to HSA via its acyl glucuronides proceeds through both transacylation (direct nucleophilic displacement) and glycation mechanisms; NAG rapidly forms an adduct that may be unstable, and the protein adduct from the 2-O-acyl glucuronide is as important for the covalent binding as those from the 1-O-acyl glucuronides.

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mentioning

confidence: 99%

In Vitro Regioselective Stability of β‐1‐O‐ and 2‐O‐Acyl Glucuronides of Naproxen and Their Covalent Binding to Human Serum Albumin

Iwaki¹,

Ogiso²,

Inagawa³

et al. 1999

Journal of Pharmaceutical Sciences

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“…This indicates that the rate of hydrolysis of Fgnd to F increased in the presence of HSA (Figures 2(b) and 3). The hydrolysis of oxaprozin acyl glucuronide to oxaprozin by HSA had also been reported [25]. Kurono et al [13,14,26] reported that HSA has several kinds of esterase-like activities.…”

Section: Reversible Binding Of Fgnd and F To Hsamentioning

confidence: 91%

Interaction of human serum albumin with furosemide glucuronide: a role of albumin in isomerization, hydrolysis, reversible binding and irreversible binding of a 1-O-acyl glucuronide metabolite

Mizuma¹,

Benet²,

Lin³

1999

Biopharm. Drug Dispos.

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“…Reversible protein binding can play a significant role in the kinetics and relative disposition of acyl glucuronides and iso-glucuronides along the various pathways of rearrangement, hydrolysis and covalent binding in vitro (and presumably in vivo) [e.g. 41,51,53,55,56]. This is important also in consideration of catalysts for hydrolysis of acyl glucuronides and isoglucuronides (Fig, 2).…”

Section: Distributionmentioning

confidence: 99%

“…For example, contrasting results on the role of albumin as a catalyst for hydrolysis of acyl glucuronides and isoglucuronides have been presented [e.g. [55][56][57].…”

Section: Distributionmentioning

confidence: 99%

Iso-glucuronides

Dickinson¹

2011

CDM

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This review on isomers or acyl glucuronides (iso-glucuronides) updates earlier reviews, and attempts to place in context the advances that have been made, especially over the last 15 years. The essential chemistry behind the intramolecular acyl migration and anomerization reactions of acyl glucuronides has been appreciated for 30 years. The great advances in the past 15 years have been in understanding the dynamics and kinetics of these processes in vitro, using highly sophisticated modern technology, e.g. LC-NMR, LC-MS/MS. In this way, earlier assumptions on kinetics and identification of migration isomers and anomers have come under intense review and update. Extensive structure-activity relationships, involving electronic and steric characteristics of an acyl glucuronide and its possible 7 isomers (excluding transient open-chain species) have been delineated. The covalent modification of endogenous proteins and other macromolecules has been further explored, though direct linkage between such modification and toxic sequelae remains elusive. An alternative view of acyl glucuronides and iso-glucuronides as just xenobiotics has perhaps added the dimension that acyl glucuronidation (and attendant formation of iso-glucuronides) does not necessarily mean that glucuronidation of the aglycone has ended metabolic sequences in vivo.

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Reactions of Oxaprozin-1-0-Acyl Glucuronide in Solutions of Human Plasma and Albumin

Cited by 47 publications

References 13 publications

In Vitro Regioselective Stability of β‐1‐O‐ and 2‐O‐Acyl Glucuronides of Naproxen and Their Covalent Binding to Human Serum Albumin

In Vitro Regioselective Stability of β‐1‐O‐ and 2‐O‐Acyl Glucuronides of Naproxen and Their Covalent Binding to Human Serum Albumin

Interaction of human serum albumin with furosemide glucuronide: a role of albumin in isomerization, hydrolysis, reversible binding and irreversible binding of a 1-O-acyl glucuronide metabolite

Iso-glucuronides

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