Reactivity of diflunisal acyl glucuronide in human and rat plasma and albumin solutions

Watt J.A. and Dickinson R.G. (1990) Reactivity of diflunisal acyl glucuronide in human and rat plasma and albumin solutions. Biochemical Pharmacology, 39 6: 1067-1075. doi:10.1016/0006-2952(90)90286-T


Author Watt J.A.
Dickinson R.G.
Title Reactivity of diflunisal acyl glucuronide in human and rat plasma and albumin solutions
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 1990-03-15
Sub-type Article (original research)
DOI 10.1016/0006-2952(90)90286-T
Volume 39
Issue 6
Start page 1067
End page 1075
Total pages 9
Subject 3004 Pharmacology
Abstract Diflunisal acyl glucuronide (DAG) is a major metabolite of diflunisal (DF) in rats and humans. We have investigated the reactivity of DAG, in purified albumin solutions and plasma from both rat and human sources, along three interrelated pathways: rearrangement via acyl migration to yield positional isomers of DAG, hydrolysis of DAG and/or its isomers to liberate DF, and formation of covalent adducts of DF (via DAG and/or its isomers) with plasma protein. Two initial concentrations of DAG (ca. 50 and 10 μg DF equivalents/mL) were used throughout. In all incubations, the order of quantitative importance of the reactions was: rearrangement > hydrolysis >covalent binding. At pH 7.4 and 37°, degradation of DAG in albumin solutions (e.g. half-life ca. 95 min in fatty acid-free human serum albumin) was retarded in comparison to that found in buffer alone (half-life ca. 35 min). Degradation in unbuffered rat and human plasma containing heparin was comparable to that found in buffer. Maximal covalent binding to protein was achieved after 4-8 hr incubation, and was greatest for fatty acid-free human serum albumin (165ng DF/mg albumin). Thereafter, slow degradation of the adducts was observed. Formation of DF-plasma protein adducts in vivo was also found in rats and humans dosed with DF.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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