Paracetamol and Pharmacogenetic

Study Overview
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Brief Summary
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Recent works has emphasized that the mechanism of action of paracetamol analgesic depend on its metabolism in the body, since a breakdown product of paracetamol, the AM404 is now considered the analgesic metabolite of paracetamol suggesting as paracetamol may be a pro-drug. Indeed, it has been shown that paracetamol may have a deleterious effect, especially in vulnerable populations (hepatic insufficiency, elderly). First results showed a very significant decrease in sulfatation and gluthatione and increased phase 1 metabolism of acetaminophen, which involves enzymes such as cytochrome P450. Multifactorial causes, combining nutrition (depletion of sulfur amino acids), increased detoxification of toxic metabolites of paracetamol, stress or trauma are discussed to explain the results. Clinical studies showed a great variability of pain assessment by patients and variability in the metabolic response of paracetamol. Genetic factors probably play a role remains largely unknown. The review of the literature on genetic polymorphism shows the involvement of a number of enzymes that are well known, predominantly on the metabolism of acetaminophen liver, but without connection with its analgesic effect. This is a critical missing link in the understanding of the analgesic effect of paracetamol.

Detailed Description
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Randomized, single-center, placebo-controlled, double-blind, cross-over in 100 healthy volunteers meeting the inclusion criteria and receiving 2g of paracetamol orally or placebo on two study periods separated by one week. The evaluation criterion is the difference in areas under the curve of pain thresholds to thermal and mechanical stimulations test

Official Title
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Paracétamol and Pharmacogenetic in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Paracetamol (drug)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers Males Aged between 18 and 30 years Exclusion Criteria: Subject without cons-indications of paracetamol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br> | Drug: Paracetamol (drug)<br>* Randomized, single-center, placebo-controlled, double-blind, cross-over in 100 healthy volunteers meeting the inclusion criteria and receiving 2g of paracetamol orally or placebo on two study periods separated by one week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between Pharmacogenetic profile and pain threshold |  | until 14 days before the administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of thermal and mechanical pain thresholds |  | until 1 hour before the administration | 
| Determination of blood concentration of gluthatione |  | until 1 hour before administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacogenetic of paracetamol, Pain threshold