Effect of maximum OTC doses of naproxen sodium or acetaminophen on low-dose aspirin inhibition of serum thromboxane B₂

Abstract

Objectives:

This study evaluated the platelet inhibitory effects of low-dose enteric-coated aspirin (EC-ASA) when used concomitantly with maximum over-the-counter (OTC) doses of naproxen sodium (NAPSO) or acetaminophen to determine whether NAPSO and acetaminophen interfere with the anti-platelet effect of aspirin.

Research design and methods:

Phase I, randomized, open-label, multi-dose, three-period, parallel group, pharmacodynamic trial conducted in healthy male and female volunteers (n = 47 randomized subjects and n = 37 evaluable subjects), mean age 40.2 years. All subjects received 5 days of EC-ASA 81 mg once daily followed by 5 days of EC-ASA 81 mg once daily alone or co-administered with either NAPSO 220 mg three times daily or acetaminophen 1 g four times daily.

Primary outcome measure:

Inhibition of serum thromboxane B₂ (TXB₂), as a marker of platelet cyclooxygenase-1 (COX-1) inhibition, measured on Day 11.

Results:

Mean inhibition of TXB₂ on Day 11 was >99% for subjects taking EC-ASA alone as well as for those who received EC-ASA co-administered with NAPSO or acetaminophen. For subjects taking EC-ASA monotherapy, mean serum TXB₂ inhibition was 99.7% (range 99.0–100%), for those taking EC-ASA with acetaminophen it was 99.6% (range 98.3–99.9%), and for those taking EC-ASA with NAPSO, mean serum TXB₂ inhibition was 99.7% (range 99.2–100%).

Study limitation:

Small sample size and open-label trial design.

Conclusions:

The anti-platelet effect of EC-ASA 81 mg once daily was maintained following its co-administration with maximum OTC doses of NAPSO or acetaminophen.

Key words::

• Acetaminophen
• Aspirin
• Ibuprofen
• Naproxen sodium
• Platelet inhibition
• Thromboxane B₂

Transparency

Declaration of funding

Bayer HealthCare, Consumer Care Division, funded the study and had a role in the study design and writing of the manuscript.

Declaration of financial/other relationships

J.O. has declared that he is an employee of Kendle Early Stage. No compensation was provided by Bayer for the preparation of this manuscript. M.C.H. has declared that he has received research support from the American College of Rheumatology, Arthritis Foundation and National Institutes of Health; and that he is a consultant to Astra Zeneca, Bayer Healthcare LLC, CombinatoRx, Endo Pharmaceuticals, Merck & Co. Inc., NicOx S.A., Novartis Pharma AG, Pfizer and Pozen Inc. M.S. has declared that he has been a consultant and speaker for Bayer HealthCare. K.B. has declared that he is a consultant, and has received research support from, sanofi-aventis, Bayer HealthCare, GlaxoSmithKline, Merck, Novartis and Pfizer.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors thank Lorraine R. Baer, PharmD for her writing and editorial assistance and Reinhard Schuller, PhD for his contribution to the statistical analysis.

Some of the data was previously presented as a poster at the 71st Annual Meeting of the American College of Rheumatology meeting, Boston, MA, November 9, 2007.