title: Parecoxib sodium, an injectable COX-2-specific inhibitor, does not affect unfractionated heparin-regulated blood coagulation parameters.
abstract: The objective of this study was to evaluate the potential for hemostatic interaction between a full analgesic dose of parecoxib sodium (parecoxib), a prodrug of the COX-2 specific inhibitor valdecoxib, and unfractionated heparin (UFH) in healthy male subjects. This open-label, single-center study comprised two treatment periods. In treatment period I, fasted, eligible subjects (n = 18) received a UFH bolus (4000 U) followed by a 36-hour UFH infusion (start dose 10-14 U/kg). Activated partial thromboplastin time (aPTT), prothrombin time (PT), and platelet counts were measured at regular intervals up to 24 hours after the end of the UFH infusion. After a 2-day washout, patients randomized to treatment period II received a full analgesic dosage of parecoxib 40 mg bid intravenously (IV) for 6 days (n = 18), with concomitant UFH (same regimen as treatment period I) on day 5 (n = 18). APTT, PT, and platelet counts were evaluated at regular intervals up to 24 hours after UFH infusion. Coadministration of parecoxib 40 mg bid IV with UFH (treatment period II) had no significant effect on aPTT, PT, or platelet counts, which were similar to those of participants receiving UFH alone (treatment period I) at all time points. These results show that a full analgesic dose of parecoxib, a COX-2-specific inhibitor available for parenteral administration, can be coadministered with UFH without affecting blood coagulation parameters. Therefore, parecoxib may be administered to patients who are receiving UFH for thromboprophylaxis.
authors.affiliation: Clinical Research Center, New Orleans, Louisiana, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Noveck
authors.forename: Richard C
authors.initials: RC
authors.lastname: Hubbard
mesh_terms: D000328:Adult; D001779:Blood Coagulation Factors; D051546:Cyclooxygenase 2; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010976:Platelet Count / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D011517:Prothrombin Time / Q000379:methods
chemical_list: D001779:Blood Coagulation Factors; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D006493:Heparin; C409945:parecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases