METABOLISM OF PRAVASTATIN SODIUM IN ISOLATED RAT HEPATOCYTES .1. GLUTATHIONE CONJUGATE FORMATION REACTION

被引：22

作者：

MURAMATSU, S

MIYAGUCHI, K

IWABUCHI, H

MATSUSHITA, Y

NAKAMURA, T

KINOSHITA, T

TANAKA, M

TAKAHAGI, H

机构：

[1] Analytical and Metabolic Research Laboratories, Sankyo Co. Ltd., Shinagawa-ku, Tokyo 140, 2-58

来源：

XENOBIOTICA | 1992年 / 22卷 / 05期

关键词：

D O I：

10.3109/00498259209053111

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The metabolic fate of pravastatin sodium (sodium (+)-(3R, 5R)-3,5-dihydroxy-7-{(1',S,2'S,6'S,8'S,8'aR)-6'-hydroxy-2'methyl-8'-[(S)-2"-methylbutyryloxy]- 1',2',6' 8'a-hexahydro-1'-naphthyl} heptanoate) was studied in isolated rat hepatocytes. 2. Two polar metabolites were isolated and identified as a glutathione conjugate and a dihydrodiol. 3. Both metabolites were formed via an epoxide which has been identified as the 4'a-beta,5'beta-epoxide on the decalin moiety. 4. Formation of the glutathione conjugate was enzymic, while the dihydrodiol was formed by non-enzymic hydrolysis of the epoxide accompanied by the intramolecular migration of the double bond.

引用

页码：487 / 498

页数：12

共 8 条

[1]

ARAI M, 1988, ANN REP SANKYO RES L, V40, P1

[2] STRUCTURE OF LEUKOTRIENE-C IDENTIFICATION OF THE AMINO-ACID PART [J].

HAMMARSTROM, S ;

MURPHY, RC ;

SAMUELSSON, B ;

CLARK, DA ;

MIOSKOWSKI, C ;

COREY, EJ .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1979, 91 (04) :1266-1272

[3]

HARUYAMA H, 1986, CHEM PHARM BULL, V34, P1459

[4]

HIROTA T, 1985, RES COMMUN CHEM PATH, V49, P435

[5]

KOMAI T, 1988, 2ND INT ISSX M KOB

[6]

Moldeus P, 1978, Methods Enzymol, V52, P60

[7] METABOLISM OF PRAVASTATIN SODIUM IN ISOLATED RAT HEPATOCYTES .2. STRUCTURE ELUCIDATION OF THE METABOLITES BY NMR-SPECTROSCOPY [J].

NAKAMURA, T ;

YODA, K ;

KUWANO, H ;

MIYAGUCHI, K ;

MURAMATSU, S ;

TAKAHAGI, H ;

KINOSHITA, T .

XENOBIOTICA, 1991, 21 (03) :277-293

[8] CS-514, A COMPETITIVE INHIBITOR OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE - TISSUE-SELECTIVE INHIBITION OF STEROL SYNTHESIS AND HYPOLIPIDEMIC EFFECT ON VARIOUS ANIMAL SPECIES [J].

TSUJITA, Y ;

KURODA, M ;

SHIMADA, Y ;

TANZAWA, K ;

ARAI, M ;

KANEKO, I ;

TANAKA, M ;

MASUDA, H ;

TARUMI, C ;

WATANABE, Y ;

FUJII, S .

BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 877 (01) :50-60

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