A Pharmacokinetic Drug Interaction and Tolerance Study of Paracetamol and Nefopam

Study Overview
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Brief Summary
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Pain remains the leading cause of consultation. Despite a wide therapeutic arsenal, a significant percentage of patients disclaim little or no pain relief with common analgesics, specific or not their type of pain. This is especially true in cases of chronic pain, and current treatments are associated with many side effects. A need for therapeutic innovation is needed. Paracetamol is currently the most widely used analgesic worldwide but despite its excellent safety, its analgesic effect is limited from moderate to severe pain. Many analgesic drug combinations include paracetamol, recently the co-administration of paracetamol and nefopam showed a supra-additive antinociceptive effect (Van Elstraete AC et al. 2013). The development of a formulation associating paracetamol and nefopam first requires searching a possible pharmacokinetic interaction between the two active substances and assessing safety of this combination in healthy volunteers. No published studies providing such information.

Detailed Description
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This is a randomised, cross-over, open label trial assessing drug interaction between paracetamol and nefopam in healthy volunteers.

Official Title
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A Pharmacokinetic Drug Interaction and Tolerance Study of Paracetamol and Nefopam

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: paracetamol 1000 mg per os, nefopam 60mg per os, paracetamol 1000 mg + nefopam 60 mg per os


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 ALT, AST, PAL, normal GGT, creatinine <133μmol / L, hematocrit>38% Informed consent to the trial Healthy volunteers affiliated to the French Social Security

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: paracetamol<br>drug interaction between paracetamol and nefopam in healthy volunteers. | Drug: paracetamol 1000 mg per os, nefopam 60mg per os, paracetamol 1000 mg + nefopam 60 mg per os<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Existence of drug interaction | Drug metabolites and principle assessing by LC / MS / MS in blood samples. Determining of Cmax, Tmax, AUC and Half-life | AT DAY 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| influence of paracetamol on the kinetics of nefopam |  | AT DAY 1 | 
| Measure of plasma pharmacokinetic parameters of each active metabolites and principles (dosage nefopam, N-desmethyl-nefopam, paracetamol, paracetamol glucuronide, paracetamol sulfate) alone |  | at day 1 | 
| Measure of plasma pharmacokinetic parameters in combination (AUC, Cmax, Tmax, half-life time of apparent elimination terminal). |  | at day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paracetamol, Nefopam, Pharmacokinetic, Drug interaction