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

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.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology*
  • Etodolac / pharmacology*
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / blood
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Prostaglandin-Endoperoxide Synthases / blood
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Thromboxane B2 / biosynthesis
  • Thromboxane B2 / blood


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Etodolac
  • Thromboxane B2
  • Prostaglandin-Endoperoxide Synthases