QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.122283v1 322/2/453    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Capone, M. L. Articles by Patrignani, P. Search for Related Content PubMed PubMed Citation Articles by Capone, M. L. Articles by Patrignani, P.

CARDIOVASCULAR

Human Pharmacology of Naproxen Sodium

Department of Medicine and Center of Excellence on Aging, School of Medicine, "G. d'Annunzio" University, Chieti, Italy (M.L.C., S.T., M.G.S., P.A., L.D.F., P.P.); "G. d'Annunzio" University Foundation, Ce.S.I., Chieti, Italy (M.L.C., S.T., M.G.S., P.A., L.D.F., P.P.); and SS Annunziata Hospital, Chieti, Italy (G.M., P.D.G.)

We compared the variability in degree and recovery from steady-state inhibition of cyclooxygenase (COX)-1 and COX-2 ex vivo and in vivo and platelet aggregation by naproxen sodium at 220 versus 440 mg b.i.d. and low-dose aspirin in healthy subjects. Six healthy subjects received consecutively naproxen sodium (220 and 440 mg b.i.d.) and aspirin (100 mg daily) for 6 days, separated by washout periods of 2 weeks. COX-1 and COX-2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity: 1) the measurement of serum thromboxane (TX)B₂ levels and whole-blood lipopolysaccharide-stimulated prostaglandin (PG)E₂ levels, markers of COX-1 in platelets and COX-2 in monocytes, respectively; 2) the measurement of urinary 11-dehydro-TXB₂ and 2,3-dinor-6-keto-PGF₁ levels, markers of systemic TXA₂ biosynthesis (mostly COX-1-derived) and prostacyclin biosynthesis (mostly COX-2-derived), respectively. Arachidonic acid (AA)-induced platelet aggregation was also studied. The maximal inhibition of platelet COX-1 (95.9 ± 5.1 and 99.2 ± 0.4%) and AA-induced platelet aggregation (92 ± 3.5 and 93.7 ± 1.5%) obtained at 2 h after dosing with naproxen sodium at 220 and 440 mg b.i.d., respectively, was indistinguishable from aspirin, but at 12 and 24 h after dosing, we detected marked variability, which was higher with naproxen sodium at 220 mg than at 440 mg b.i.d. Assessment of the ratio of inhibition of urinary 11-dehydro-TXB₂ versus 2,3-dinor-6-keto-PGF₁ showed that the treatments caused a more profound inhibition of TXA₂ than prostacyclin biosynthesis in vivo throughout dosing interval. In conclusion, neither of the two naproxen doses mimed the persistent and complete inhibition of platelet COX-1 activity obtained by aspirin, but marked heterogeneity was mitigated by the higher dose of the drug.

Address correspondence to: Dr. Paola Patrignani, Sezione di Farmacologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Università di Chieti "G. d'Annunzio", Via dei Vestini, 31, 66013 Chieti, Italy. E-mail: ppatrignani{at}unich.it

This article has been cited by other articles:

				C. Patrono and C. Baigent Low-Dose Aspirin, Coxibs, and other NSAIDS: A Clinical Mosaic Emerges Mol. Interv., February 1, 2009; 9(1): 31 - 39. [Abstract] [Full Text] [PDF]

				L. A. Garcia Rodriguez, S. Tacconelli, and P. Patrignani Role of Dose Potency in the Prediction of Risk of Myocardial Infarction Associated With Nonsteroidal Anti-Inflammatory Drugs in the General Population J. Am. Coll. Cardiol., November 11, 2008; 52(20): 1628 - 1636. [Abstract] [Full Text] [PDF]