Abstract
Purpose: Both isoforms of cyclo-oxygenase, COX-1 and COX-2, are inhibited to varying
degrees by all of the available nonsteroidal anti-inflammatory drugs (NSAIDs). Because
inhibition of COX-1 by NSAIDs is linked to gastrointestinal ulcer formation, those
drugs that selectively inhibit COX-2 may have less gastrointestinal toxicity. We measured
the extent to which NSAIDs and other anti-inflammatory or analgesic drugs inhibit
COX-1 and COX-2 in humans.
Subjects and Methods: Aliquots of whole blood from 16 healthy volunteers were incubated
ex vivo with 25 antiinflammatory or analgesic drugs at six concentrations ranging from 0
(control) to 100 μM (n = 5 for each). Blood was assayed for serum-generated thromboxane
B2 synthesis (COX-1 assay) and for lipopolysaccharide-stimulated prostaglandin E2 synthesis (COX-2 assay). In addition, gastric biopsies from the same volunteers were
incubated with each drug ex vivo and mucosal prostaglandin E2 synthesis measured.
Results: Inhibitory potency and selectivity of NSAIDs for COX-1 and COX-2 activity
in blood varied greatly. Some NSAIDs (eg, flurbiprofen, ketoprofen) were COX-1 selective,
some (eg, ibuprofen, naproxen) were essentially nonselective, while others (eg, diclofenac,
mefenamic acid) were COX-2 selective. Inhibitory effects of NSAIDs on gastric prostaglandin
E2 synthesis correlated with COX-1 inhibitory potency in blood (P <0.001) and with COX-1 selectivity (P <0.01), but not with COX-2 inhibitory potency. Even COX-2 “selective” NSAIDs still
had sufficient COX-1 activity to cause potent inhibitory effects on gastric prostaglandin
E2 synthesis at concentrations achieved in vivo.
Conclusion: No currently marketed NSAID, even those that are COX-2 selective, spare
gastric COX activity at therapeutic concentrations. Thus, all NSAIDs should be used
cautiously until safer agents are developed.
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Article info
Publication history
Published online: August 16, 2004
Accepted:
February 25,
1998
Received in revised form:
February 25,
1998
Received:
October 2,
1997
Footnotes
☆Supported by a Merit Review Grant from the Department of Veterans Affairs and Southland Financial Corporation Distinguished Chair in Geriatrics.
Identification
Copyright
© 1998 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
