Stereospecific pH-dependent degradation kinetics of R- and S-naproxen-beta-l-O-acyl-glucuronide.
Chirality
; 14(4): 305-12, 2002 May 05.
Article
em En
| MEDLINE
| ID: mdl-11968070
ABSTRACT
The hydrolysis and acyl migration of biosynthetic S-naproxen-beta-l-O-acyl glucuronide (I) and R-naproxen-beta-l-O-acyl glucuronide (II) was followed by HPLC. Nine first-order kinetic rate constants for the hydrolysis and acyl migration between the beta-l-O-acyl glucuronide, its alpha/beta-2, alpha/beta-3-, alpha/beta-4-, and alpha-1-O-acyl isomers and naproxen aglycone were determined for I and II at pH 7.00, 7.40 and 8.00 at 37 degrees C by kinetic simulation. For I the 3-O-acyl isomer was the most stable isomer as the pseudo-equilibrium ratio for the major acyl-migrated isomers was 11.50.9 (2-O-acyl isomer3-O-acyl isomer4-O-acyl isomer). The 3- and 4-O-acyl isomers of II were equally stable as the pseudo-equilibrium ratio for the major acyl-migrated isomers was 11.41.4 (2-O-acyl isomer3-O-acyl isomer4-O-acyl isomer). For both I and II, the pseudo-equilibrium ratio between the major 2-O-acyl isomer and the minor alpha-l-O-acyl isomer was 101 (2-O-acyl isomeralpha-l-O-acyl isomer). The pseudo-equilibrium found for the major acyl-migrated isomers of I and II in the present study corresponds with the pattern previously published for R- and S-ketoprofen-beta-l-O-acyl glucuronide acyl-migrated isomers, suggesting that these findings may be general for acyl-migrated beta-l-O-acyl glucuronides of enantiomeric 2-arylpropionic acids.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cetoprofeno
/
Naproxeno
/
Glucuronídeos
Limite:
Animals
Idioma:
En
Revista:
Chirality
Assunto da revista:
BIOLOGIA MOLECULAR
/
QUIMICA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Dinamarca