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

被引：148

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

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