Effect of Ibuprofen, Paracetamol and Their Combination on Radical Oxygen Species (ROS) Production

Study Overview
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Brief Summary
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The purpose of this study is to determine whether paracetamol, ibuprofen or their combination can modify generation of radical oxygen species (ROS) from stimulated neutrophils.

Detailed Description
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Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate clinical inflammatory symptoms (e.g. pain, swelling and reduced function). Leukocytes, upon activation during inflammatory states, generate radical oxygen species (ROS) which primarily are intended for host defence against invading pathogens. Certain NSAID can modify the generation of ROS from stimulated neutrophils ranging form increased production to reduced production. Preliminary experiments in our laboratory have shown that different NSAIDs have opposing effects on the ability of leukocytes (granulocytes and monocytes) to produce ROS upon a standardized stimulus, i.e. phorbol myristate acetate (PMA). Paracetamol has a marked inhibitory effect and ibuprofen has a facilitating effect on ROS production. An inhibitory effect of paracetamol was also seen when examining platelet activation markers, whereas acetylsalicylic acid showed a clear enhancing effect in this respect. We want to examine if intake of paracetamol or ibuprofen in vivo have similar effects on leukocyte ROS production and platelet activation, respectively.

Official Title
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The Effect of Ibuprofen, Paracetamol and Their Combination on Reactive Oxygen Species (ROS)- Production in Leukocytes and Platelet Activation

Conditions
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Pain

Intervention / Treatment
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* Drug: Ibuprofen
* Drug: Ibuprofen
* Drug: Paracetamol (acetaminophen) 1000 mg
* Drug: Paracetamol + ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers of both sexes (ASA type I). Females who are not pregnant or plan conception. (A pregnancy test will be conducted before each test day) Persons who have not used analgesics for 3 days prior to the blood sampling. Persons without known active peptic ulcer or gastrointestinal bleeding. Persons without any known hypersensitivity for NSAIDs. Persons under no other drug treatment than contraceptives. Age 18 to 35 years of Caucasian origin Exclusion Criteria: Pregnancy during the test period. Development of active peptic ulcer during the test period. Change in medication status during the test period (after inclusion).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ibuprofen 400 mg<br>Ibuprofen oral single dose | Drug: Ibuprofen<br>* Tablet ibuprofen 400 mg oral single dose (1 tablet)<br>* Other names: ATC code: M01A E01;|
| Active Comparator: Ibuprofen 1200 mg<br>Ibuprofen oral single dose | Drug: Ibuprofen<br>* Tablets (2 x 600 mg) oral single dose (2 tablets)<br>* Other names: ATC code: M01A E01;|
| Active Comparator: Paracetamol (acetaminophen) 1000 mg<br>Paracetamol (acetaminophen) oral single dose | Drug: Paracetamol (acetaminophen) 1000 mg<br>* Tablets (2 x 500 mg) oral single dose (2 tablets)<br>* Other names: ATC code: N02B E01;|
| Active Comparator: Ibuprofen 400 mg + paracetamol 1000 mg<br>Paracetamol (acetaminophen) + ibuprofen oral single dose | Drug: Paracetamol + ibuprofen<br>* Tablets (ibuprofen 400 mg + paracetamol (acetaminophen) 2 x 500 mg) single oral dose (3 tablets)<br>* Other names: ATC code: N02B E01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukocyte radical oxygen species (ROS) production |  | 24 hours for each crossover event | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet activation status |  | 24 hours for each crossover event | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetaminophen, Ibuprofen, Platelets, Leukocytes, Oxygen species, Humans, Blood Platelets, Reactive Oxygen Species, Platelet Activation