ETODOLAC SELECTIVELY INHIBITS HUMAN PROSTAGLANDIN-G/H-SYNTHASE-2 (PGHS-2) VERSUS HUMAN PGHS-1

被引：147

作者：

GLASER, K

SUNG, ML

ONEILL, K

BELFAST, M

HARTMAN, D

CARLSON, R

KREFT, A

KUBRAK, D

HSIAO, CL

WEICHMAN, B

机构：

[1] Wyeth-Ayerst Research, Princeton, NJ 08543-8000

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1995年 / 281卷 / 01期

关键词：

PROSTAGLANDIN G/H SYNTHASE (CYCLOOXYGENASE); WHOLE BLOOD; HUMAN; ETODOLAC; NAPROXEN; DICLOFENAC; TENIDAP;

D O I：

10.1016/0014-2999(95)00302-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The isozymes of prostaglandin G/H synthase (PGHS) are shown to be differentially inhibited in vitro by currently marketed nonsteroidal anti-inflammatory drugs (NSAIDs) using microsomal rhPGHS-1 and rhPGHS-2. Comparison of selectivity ratios (IC50 rhPGHS-1/IC50 rhPGHS-2) demonstrated a 10-fold selectivity of etodolac (Lodine) for rhPGHS-2, whereas the other NSAIDs evaluated demonstrated no preference or a slight preference for inhibition of rhPGHS-1. In vitro enzyme results were supported by a human whale blood assay where etodolac also demonstrated a 10-fold selectivity for inhibition of PGHS-2 mediated TxB(2) production. Taken together, these data may be key to explaining the clinically observed gastrointestinal safety of etodolac versus other marketed NSAIDs.

引用

页码：107 / 111

页数：5

共 16 条

[1] ADAMS L, 1990, GASTROENTEROLOGY, V98, pA11
[2] Arnold JD, 1991, J MUSCULOSKEL MED, V8, pS54
[3] PURIFICATION, CHARACTERIZATION AND SELECTIVE-INHIBITION OF HUMAN PROSTAGLANDIN-G/H SYNTHASE-1 AND SYNTHASE-2 EXPRESSED IN THE BACULOVIRUS SYSTEM
BARNETT, J
CHOW, J
IVES, D
CHIOU, M
MACKENZIE, R
OSEN, E
NGUYEN, B
TSING, S
BACH, C
FREIRE, J
CHAN, H
SIGAL, E
RAMESHA, C
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1994, 1209 (01): : 130 - 139
[4] HUMAN CYCLOOXYGENASE-2 CDNA
HLA, T
NEILSON, K
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (16) : 7384 - 7388
[5] HUMBER LG, 1992, DRUGS TODAY, V29, P265
[6] EFFECT OF ETODOLAC ON PROSTAGLANDIN E(2) BIOSYNTHESIS, ACTIVE OXYGEN GENERATION AND BRADYKININ FORMATION
INOUE, K
MOTONAGA, A
DAINAKA, J
NISHIMURA, T
HASHII, H
YAMATE, K
UEDA, F
KIMURA, K
[J]. PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 1994, 51 (06): : 457 - 462
[7] JONES DA, 1993, J BIOL CHEM, V268, P9049
[8] KUJUBU DA, 1992, J BIOL CHEM, V267, P7991
[9] LAINE L, 1995, IN PRESS GASTROINTES
[10] LANEUVILLE O, 1994, J PHARMACOL EXP THER, V271, P927

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