Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs.

Article Details


Cryer B, Feldman M

Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs.

Am J Med. 1998 May;104(5):413-21.

PubMed ID
9626023 [ View in PubMed

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 microM (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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Mefenamic acidProstaglandin G/H synthase 1ProteinHumans
Mefenamic acidProstaglandin G/H synthase 2ProteinHumans
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetaminophenProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
Acetylsalicylic acidProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
EtodolacProstaglandin G/H synthase 2Ki (nM)2470N/AN/ADetails
FenoprofenProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
FlurbiprofenProstaglandin G/H synthase 2Ki (nM)4230N/AN/ADetails
IbuprofenProstaglandin G/H synthase 2Ki (nM)9900N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2Ki (nM)370N/AN/ADetails
KetoprofenProstaglandin G/H synthase 2Ki (nM)880N/AN/ADetails
KetorolacProstaglandin G/H synthase 2Ki (nM)180N/AN/ADetails
Mefenamic acidProstaglandin G/H synthase 2Ki (nM)160N/AN/ADetails
NabumetoneProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
NaproxenProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
NimesulideProstaglandin G/H synthase 2Ki (nM)180N/AN/ADetails
OxaprozinProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
Salicylic acidProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
SalsalateProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
SulindacProstaglandin G/H synthase 2Ki (nM)>10000N/AN/ADetails
TolmetinProstaglandin G/H synthase 2Ki (nM)2250N/AN/ADetails