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SAT0058 The novel cox-2 specific inhibitor, valdecoxib, does not affect platelet function in healthy adults
  1. PT Leese1,
  2. D Recker2,
  3. ME Kuss2
  1. 1Medical Scientific Services, Quintiles Phase I Services, Lenexa
  2. 2Research and Development, Pharmacia Corporation, Skokie, USA

Abstract

Background Conventional NSAIDs have traditionally been used to manage pain and inflammation; however, as nonspecific inhibitors of cyclooxygenase (COX-1 and COX-2), they are associated with significant adverse events, including impaired platelet function.

Objectives The purpose of this study was to compare the effect of valdecoxib, a new COX-2 specific inhibitor, on platelet aggregation and bleeding time to that of the conventional NSAIDs, naproxen and diclofenac.

Methods This was a single-centre, double-blind, randomised comparison of valdecoxib 40 mg BID, naproxen 500 mg BID, diclofenac 75 mg BID, and placebo in healthy adult subjects. Sixty-two subjects received active medication or placebo for 7.5 days. Platelet aggregation responses to arachidonate (AA), collagen, and adenosine diphosphate (ADP); Simplate II bleeding times; and serum thromboxane (Tx) B2 concentrations were measured at baseline; 30 min predose, 2, 4, and 8 h postdose on Day 1; and 2, 4, and 8 h after the final dose on Day 8.

Results Valdecoxib produced no observable effects on Days 1 and 8 on platelet aggregation responses to AA, collagen, or ADP. Compared to placebo, valdecoxib produced no significant differences at any assessment. In contrast, naproxen significantly reduced all three platelet aggregation responses compared to placebo at most assessment times. The diclofenac group experienced significant reductions in AA-induced platelet aggregation compared to placebo at most assessment times, with fewer significant changes observed in response to collagen and ADP. Valdecoxib also had no effect on bleeding time compared to placebo (p > = 0.136). Serum TxB2 was not significantly altered from baseline for either valdecoxib or placebo at any assessment time (p > = 0.267), while significant differences from baseline were seen for naproxen at all assessment times when compared to placebo (p < = 0.002).

Abstract SAT0058 Table 1

Conclusion The lack of effect on platelet aggregation and bleeding time would suggest that valdecoxib will have an improved clinical safety profile over conventional NSAIDs, particularly in patients for whom bleeding complications are a concern.

Sponsored by Pharmacia Corporation and Pfizer, Inc.

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