title: Effects of meloxicam and indomethacin on cyclooxygenase pathways in healthy volunteers.
abstract: BACKGROUND
  Meloxicam is a new NSAID with selectivity for the inducible cyclooxygenase (COX-2) in vitro. We compared the effects of therapeutically equivalent doses of meloxicam and indomethacin, a preferential inhibitor of the constitutive cyclooxygenase (COX-1), on platelet aggregation and platelet thromboxane formation, which are exclusively COX-1 dependent, physiological renal, and total body prostaglandin E2 (PGE2) production.
  
  
  METHODS
  In a randomized cross-over design, 14 healthy female volunteers received meloxicam 7.5 mg per day for 6 days or indomethacin 25 mg three times per day for 3 days; the wash-out period was 5 days, and drug intake was adapted to the menstrual cycle. On the day before treatment and on the last day of each treatment period the following parameters were evaluated: maximum platelet aggregation and thromboxane B2 (TXB2) formation in response to 1.0 mmol/L arachidonic acid; 24-hour urinary excretion of PGE2 and 7 alpha-hydroxy-5, 11-diketo-tetranor-prosta-1, 16-dionic acid (PGE-M), the index metabolites of renal and total body PGE2 synthesis, respectively, were assessed by gas chromatography/tandem mass spectrometry.
  
  
  RESULTS
  Maximum platelet aggregation and TXB2 formation were almost completely inhibited by indomethacin (-87% and -99%, respectively; p < 0.001, each) as compared to control (100%), but remained unaffected by meloxicam (-1% and +4%, respectively). Meloxicam showed no significant effects on urinary PGE2 excretion (-13%) and only slight effects on PGE-M excretion (-22%; p < 0.05), whereas indomethacin reduced urinary PGE2 excretion (-43%; p < 0.05) as well as PGE-M excretion (-36%; p < 0.001).
  
  
  CONCLUSIONS
  Our data show, that meloxicam 7.5 mg per day is COX-1 sparing in humans in vivo.
authors.affiliation: Institute of Clinical Pharmacology, Hannover Medical School, Germany.
authors.forename: D O
authors.initials: DO
authors.lastname: Stichtenoth
authors.forename: B
authors.initials: B
authors.lastname: Wagner
authors.forename: J C
authors.initials: JC
authors.lastname: Frölich
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D000077239:Meloxicam; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011453:Prostaglandins / Q000652:urine; D013810:Therapeutic Equivalency; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013843:Thiazines; D013844:Thiazoles; D013929:Thromboxane B2; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077239:Meloxicam; D007213:Indomethacin