Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects

• Published in: Journal of the American College of Cardiology Vol. 45; no. 8; pp. 1295 - 1301
• Main Authors: Capone, Marta L., Sciulli, Maria G., Tacconelli, Stefania, Grana, Marilena, Ricciotti, Emanuela, Renda, Giulia, Di Gregorio, Patrizia, Merciaro, Gabriele, Patrignani, Paola
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 19.04.2005; Elsevier Science; Elsevier Limited
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anticoagulants; Arthritis - drug therapy; Aspirin; Aspirin - administration & dosage; Aspirin - pharmacology; Biological and medical sciences; Biosynthesis; Cardiology; Cardiology. Vascular system; Cardiovascular Diseases - drug therapy; Cyclooxygenase 1; Drug dosages; Drug Interactions; Drug therapy; Drug Therapy, Combination; Enzymes; Family medical history; Heart attacks; Humans; In Vitro Techniques; Medical sciences; Membrane Proteins; Naproxen - pharmacology; Nonsteroidal anti-inflammatory drugs; Platelet Aggregation - drug effects; Prostaglandin-Endoperoxide Synthases; Studies; Thromboxane B2 - antagonists & inhibitors; AA; TX; NANSAIDs; CI; NSAIDs; IC50; PG; BID; COX; Human; Acetylsalicylic acid; Healthy subject; Pharmacokinetics; Low dose
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.01.045

We investigated the occurrence of pharmacodynamic interaction between low-dose aspirin and naproxen. The uncertainty of cardioprotection by naproxen has encouraged its combination with aspirin in patients with arthritis and cardiovascular disease. The incubation of washed platelets with naproxen for 5 min before the addition of aspirin reduced the irreversible inhibition of thromboxane (TX)B2production 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. The inhibition of serum TXB2production (index of platelet cyclooxygenase [COX]-1 activity) and platelet aggregation ex vivo and urinary 11-dehydro-TXB2levels (index of TXB2biosynthesis 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 TXB2production 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. 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.