In vitro regioselective stability of β-1-O and 2-O-acyl glucuronides of naproxen and their covalent binding to human serum albumin

被引:30
作者
Iwaki, M [1 ]
Ogiso, T [1 ]
Inagawa, S [1 ]
Kakehi, K [1 ]
机构
[1] Kinki Univ, Fac Pharmaceut Sci, Osaka 5778502, Japan
关键词
D O I
10.1021/js9802704
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 degrees C. 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 (k(d) = 2.08 +/- 0.08 h(-1)) was four times less stable than 2-isomer (k(d) = 0.51 +/- 0.02 h(-1)). NAG was degraded by hydrolysis (k(hyd) 1.01 +/- 0.10 h(-1)) and isomerization (k(iso) = 1.07 +/- 0.07 h(-1)) to the same extent; however, hydrolysis was predominant for the 2-isomer (k(d) = 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.
引用
收藏
页码:52 / 57
页数:6
相关论文
共 33 条
[1]  
BENET LZ, 1988, CELLULAR MOL ASPECTS, V173, P261
[2]  
BENET LZ, 1993, LIFE SCI, V53, P141
[3]   Stereoselective binding properties of naproxen glucuronide diastereomers to proteins [J].
Bischer, A ;
ZiaAmirhosseini, P ;
Iwaki, M ;
McDonagh, AF ;
Benet, LZ .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1995, 23 (04) :379-395
[4]   STUDIES OF INTRAMOLECULAR REARRANGEMENTS OF ACYL-LINKED GLUCURONIDES USING SALICYLIC-ACID, FLUFENAMIC ACID, AND (S)-BENOXAPROFEN AND (R)-BENOXAPROFEN AND CONFIRMATION OF ISOMERIZATION IN ACYL-LINKED DELTA-9-11-CARBOXYTETRAHYDROCANNABINOL GLUCURONIDE [J].
BRADOW, G ;
KAN, LS ;
FENSELAU, C .
CHEMICAL RESEARCH IN TOXICOLOGY, 1989, 2 (05) :316-324
[5]   STUDIES ON THE REACTIVITY OF ACYL GLUCURONIDES .2. INTERACTION OF DIFLUNISAL ACYL GLUCURONIDE AND ITS ISOMERS WITH HUMAN SERUM-ALBUMIN INVITRO [J].
DICKINSON, RG ;
KING, AR .
BIOCHEMICAL PHARMACOLOGY, 1991, 42 (12) :2301-2306
[6]   STUDIES ON THE REACTIVITY OF ACYL GLUCURONIDES .7. SALICYLIC ACYL GLUCURONIDE REACTIVITY IN-VITRO AND COVALENT BINDING OF SALICYLIC-ACID TO PLASMA-PROTEIN OF HUMANS TAKING ASPIRIN [J].
DICKINSON, RG ;
BAKER, PV ;
KING, AR .
BIOCHEMICAL PHARMACOLOGY, 1994, 47 (03) :469-476
[7]   EVIDENCE FOR COVALENT BINDING OF ACYL GLUCURONIDES TO SERUM-ALBUMIN VIA AN IMINE MECHANISM AS REVEALED BY TANDEM MASS-SPECTROMETRY [J].
DING, A ;
OJINGWA, JC ;
MCDONAGH, AF ;
BURLINGAME, AL ;
BENET, LZ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (09) :3797-3801
[8]  
DUBOIS N, 1993, DRUG METAB DISPOS, V21, P617
[10]   STUDIES ON THE IN-VITRO REACTIVITY OF CLOFIBRYL AND FENOFIBRYL GLUCURONIDES - EVIDENCE FOR PROTEIN-BINDING VIA A SCHIFF-BASE MECHANISM [J].
GRUBB, N ;
WEIL, A ;
CALDWELL, J .
BIOCHEMICAL PHARMACOLOGY, 1993, 46 (03) :357-364