Glaser K, Sung M L, O'Neill K, Belfast M, Hartman D, Carlson R, Kreft A, Kubrak D, Hsiao C L, Weichman B
Wyeth-Ayerst Research, Princeton, NJ 08543-8000, USA.
Eur J Pharmacol. 1995 Jul 25;281(1):107-11. doi: 10.1016/0014-2999(95)00302-2.
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.
