Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1.

K Glaser, M L Sung, K O'Neill, M Belfast, D Hartman, R Carlson, A Kreft, D Kubrak, C L Hsiao, B Weichman

Wyeth-Ayerst Research, Princeton, NJ 08543-8000, USA.

European journal of pharmacology 1995 Jul 25

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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 whole blood assay where etodolac also demonstrated a 10-fold selectivity for inhibition of PGHS-2 mediated TxB2 production. Taken together, these data may be key to explaining the clinically observed gastrointestinal safety of etodolac versus other marketed NSAIDs.

Citation

K Glaser, M L Sung, K O'Neill, M Belfast, D Hartman, R Carlson, A Kreft, D Kubrak, C L Hsiao, B Weichman. Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. European journal of pharmacology. 1995 Jul 25;281(1):107-11