Clinical pharmacology of platelet, monocyte, and vascular cyclooxygenase inhibition by naproxen and low-dose aspirin in healthy subjects.
BACKGROUND
The current controversy on the potential cardioprotective effect of naproxen prompted us to evaluate the extent and duration of platelet, monocyte, and vascular cyclooxygenase (COX) inhibition by naproxen compared with low-dose aspirin.


RESULTS
We performed a crossover, open-label study of low-dose aspirin (100 mg/d) or naproxen (500 mg BID) administered to 9 healthy subjects for 6 days. The effects on thromboxane (TX) and prostacyclin biosynthesis were assessed up to 24 hours after oral dosing. Serum TXB2, plasma prostaglandin (PG) E2, and urinary 11-dehydro-TXB2 and 2,3-dinor-6-keto-PGF(1alpha) were measured by previously validated radioimmunoassays. The administration of naproxen or aspirin caused a similar suppression of whole-blood TXB2 production, an index of platelet COX-1 activity ex vivo, by 94+/-3% and 99+/-0.3% (mean+/-SD), respectively, and of the urinary excretion of 11-dehydro-TXB2, an index of systemic biosynthesis of TXA2 in vivo, by 85+/-8% and 78+/-7%, respectively, that persisted throughout the dosing interval. Naproxen, in contrast to aspirin, significantly reduced systemic prostacyclin biosynthesis by 77+/-19%, consistent with differential inhibition of monocyte COX-2 activity measured ex vivo.


CONCLUSIONS
The regular administration of naproxen 500 mg BID can mimic the antiplatelet COX-1 effect of low-dose aspirin. Naproxen, unlike aspirin, decreased prostacyclin biosynthesis in vivo.
Capone
Marta L
ML
Department of Medicine and Center of Excellence on Aging, G. d'Annunzio University, School of Medicine, and G. d'Annunzio University Foundation, Chieti, Italy.
Tacconelli
Stefania
S
Sciulli
Maria G
MG
Grana
Marilena
M
Ricciotti
Emanuela
E
Minuz
Pietro
P
Di Gregorio
Patrizia
P
Merciaro
Gabriele
G
Patrono
Carlo
C
Patrignani
Paola
P
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives* / Q000652:urine; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D009288:Naproxen / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D044062:Prostaglandins I / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine
D002316:Cardiotonic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D044062:Prostaglandins I; D013929:Thromboxane B2; D009288:Naproxen; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin