Mechanisms of Action of Acetaminophen

Summary

This research study investigates whether the ability of aspirin to reduce the risk of heart attacks may be diminished by the administration of acetaminophen. Patients who have heart disease are often prescribed aspirin because of its unique ability to permanently prevent platelets from aggregating and forming a blood clot. Such blood clots cause heart attacks when they form in a blood vessel that supplies the heart with oxygen rich blood. Some of these same patients also take acetaminophen everyday for relief from arthritis pain. Higher doses of acetaminophen may also have the ability to prevent the platelets from clotting, however only temporarily. Therefore, this study evaluates whether the timing of the administration of acetaminophen (before or after aspirin) interferes with the permanent blood clotting effects of aspirin.

The primary hypothesis is that acetaminophen given two hours before aspirin will antagonize the effects of aspirin, while reversing the order of administration will not.

Conditions

• Myocardial Infarction
• Arthritis

Interventions

DRUG

Aspirin First

Crossover period Aspirin First: Subjects will receive 81 mg aspirin at approximately 8 am followed by acetaminophen at approximately 10 am.

DRUG

Aspirin Last

Crossover period Aspirin Last: Subjects will receive acetaminophen at approximately 8 am followed by 81 mg aspirin at approximately 10 am.

DRUG

Acetaminophen 1000 mg/d

Subjects will receive a daily oral dose of 1000 mg acetaminophen for six days each administered at 8 AM.

DRUG

Acetaminophen 4000 mg/d

Crossover period Acetaminophen 4000 mg/d: Acetaminophen (1000 mg p.o.) orally at 8 AM, 2 PM, 8 PM and 2 AM for 3 days. The last dose will be administered on day four at 8 AM.

DRUG

Ibuprofen 800 mg/d

Crossover period Ibuprofen 800 mg/d: Ibuprofen (200 mg) orally at at 8 AM, 2 PM, 8 PM and 2 AM for 3 days. The last dose will be administered on day four at 8 AM.

Sponsors & Collaborators

• University of Pennsylvania

  lead OTHER

Principal Investigators

• Garret A. FitzGerald, MD · University of Pennsylvania, Institute for Translationals Medicine and Therapeutics

• Susanne Fries, MD · University of Pennsylvania, Institute for Translationals Medicine and Therapeutics

• Tilo Grosser, MD · University of Pennsylvania, Institute for Translationals Medicine and Therapeutics

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2004-06-02

Primary Completion

2012-01-24

Completion

2012-01-24

Countries

• United States

Study Locations