Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects.
OBJECTIVE
We investigated the occurrence of pharmacodynamic interaction between low-dose aspirin and naproxen.


BACKGROUND
The uncertainty of cardioprotection by naproxen has encouraged its combination with aspirin in patients with arthritis and cardiovascular disease.


METHODS
The incubation of washed platelets with naproxen for 5 min before the addition of aspirin reduced the irreversible inhibition of thromboxane (TX)B(2) production by aspirin. The pharmacodynamic interaction between the two drugs was then investigated in four healthy volunteers who received aspirin (100 mg daily) for 6 days and then the combination of aspirin and naproxen for further 6 days: aspirin 2 h before naproxen (500 mg, twice-daily dosing). After 14 days of washout, naproxen was given 2 h before aspirin for further 6 days.


RESULTS
The inhibition of serum TXB(2) production (index of platelet cyclooxygenase [COX]-1 activity) and platelet aggregation ex vivo and urinary 11-dehydro-TXB(2) levels (index of TXB(2) biosynthesis in vivo) by aspirin alone (99 +/- 0.2%, 95 +/- 0.6%, and 81 +/- 4%, respectively) was not significantly altered by the co-administration of naproxen, given either 2 h after aspirin or in reverse order. In a second study, the concurrent administration of a single dose of aspirin and naproxen did not affect platelet TXB(2) production and aggregation at 1 h after dosing, when aspirin alone causes maximal inhibitory effect. Moreover, the rapid recovery of platelet COX-1 activity and function supports the occurrence of a pharmacodynamic interaction between naproxen and aspirin.


CONCLUSIONS
Naproxen interfered with the inhibitory effect of aspirin on platelet COX-1 activity and function. This pharmacodynamic interaction might undermine the sustained inhibition of platelet COX-1 that is necessary for aspirin's cardioprotective effects.
Capone
Marta L
ML
Department of Medicine and Center of Excellence on Aging, School of Medicine, G. d'Annunzio University, Chieti, Italy.
Sciulli
Maria G
MG
Tacconelli
Stefania
S
Grana
Marilena
M
Ricciotti
Emanuela
E
Renda
Giulia
G
Di Gregorio
Patrizia
P
Merciaro
Gabriele
G
Patrignani
Paola
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy; D051545:Cyclooxygenase 1; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins; D009288:Naproxen / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D013929:Thromboxane B2; D009288:Naproxen; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin