A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers.
OBJECTIVE
To compare the effects of nabumetone and meloxicam, two cyclo-oxygenase-2 (COX-2) preferential nonsteroidal anti-inflammatory drugs (NSAIDs), on platelet COX-1 activity and platelet function.


METHODS
Twelve healthy volunteers (3 male, 9 female, median age 22 years) participated in an open, randomized, cross-over trial of nabumetone 1000 mg twice daily vs meloxicam 7.5 mg twice daily during 1 week with 2 weeks wash-out. After a second 2 week wash-out period, one dose of indomethacin 50 mg was given as a positive control to check for NSAID induced inhibition of platelet function. COX-1 inhibition was measured as percentage inhibition of serum TXB2 generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100. Data are reported as median with range. Paired variables were analysed using Wilcoxons signed rank test.


RESULTS
TXB2 levels decreased significantly after all three medications, but percentage inhibition after nabumetone and indomethacin (88% and 97%, respectively) was significantly higher than after meloxicam (63%) (P<0.05). Closure times increased significantly after administration of all three medications (P<0.05). Increases in closure time after administration did not differ between nabumetone and meloxicam (24% and 14%, respectively), but were significantly larger after indomethacin administration (63%) (P<0.01).


CONCLUSIONS
In the maximum registered dosage, nabumetone inhibits thromboxane production much more than meloxicam, signifying less COX-2 selectivity of the former. However, both nabumetone and meloxicam cause only minor impairment in platelet function in comparison with indomethacin and the difference between them is not significant.
van Kraaij
D J W
DJ
Department of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands. Dvankraaij@hotmail.com
Hovestad-Witterland
A H I
AH
de Metz
M
M
Vollaard
E J
EJ
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002074:Butanones / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D008565:Membrane Proteins; D000077430:Nabumetone; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013843:Thiazines / Q000009:adverse effects / Q000494:pharmacology*; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013843:Thiazines; D013844:Thiazoles; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077430:Nabumetone; D000077239:Meloxicam