N-acetylcysteine prevents glutathione decrease and does not interfere with paracetamol antinociceptive effect at therapeutic dosage: a randomized double-blind controlled trial in healthy subjects

Paracetamol (APAP) may lead to hepatic changes even at therapeutic dosages. Glutathione (GSH) plays a pivotal role in APAP metabolism as it allows the detoxification of a toxic metabolite. N-Acetylcysteine (NAC) is APAP antidote, is also largely used as a mucoactive drug and is often associated with APAP. This study aims at evaluating if 1- NAC modifies APAP pain efficacy and 2- NAC prevents glutathione depletion with APAP at therapeutic doses. This double-blind randomized controlled study (NCT02206178) was carried out in 24 healthy volunteers. APAP was given for 4 days (1 gram x4 daily) with NAC or with placebo. Thermal pain tests, whole blood GSH and hepatic enzymes (ASAT, ALAT) were measured before (D0) and after (D4) oral APAP-NAC or APAP-placebo intake. ANOVA for repeated measures adapted to cross-overdesign was performed and a two-tailed type I error was fixed at 5%. The primary endpoint was the area under the curve (0-240min) of pain intensity (Numerical Scale) after thermal pain stimulation using Pathway-Medoc((R)) . APAP antinociceptive effect was similar in both groups. GSH was maintained to its baseline value in the APAP/NAC group but diminished in the APAP/placebo group (p=0.033). This study shows for the first time that APAP antinociceptive effectiveness is not influenced by NAC. It also shows that the effect of APAP at therapeutic dosage on GSH may be counteracted by NAC. These issues are particularly important for patients as APAP is often prescribed for years as a first-line pain treatment and further trials in patients are now warranted. This article is protected by copyright. All rights reserved

Effet d’un polyphénol dans l’hémochromatose et l’hépatosidérose dysmétabolique : étude contrôlée randomisée

Effet d’un polyphénol dans l’hémochromatose et l’hépatosidérose dysmétabolique : étude contrôlée randomisée. 79. Congrès SNFM

Dextromethorphan Analgesia in a Human Experimental Model of Hyperalgesia

International audienc

Barriers and motivations for participation in preventive vaccine clinical trials: Experience of 5 clinical research sites

International audienc

Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): a propensity-matched analysis.

International audienc

Harmonisation of ethics committees' practice in 10 European countries

The Directive 2001/20/EC was an important first step towards consistency in the requirements and processes for clinical trials across Europe. However, by applying the same rules to all types of drug trials and transposing the Directive’s principles into pre-existing national legislations, the Directive somewhat failed to meet its facilitation and harmonisation targets. In the field of ethics, the Directive 2001/20/EC conditioned the way of understanding and transposing the “single opinion” process in each country. This led to a situation in which two models of research ethics committees organisation systems exist, being the model in which the “single opinion” is considered to be the decision made by a single ethics committee more effective and simpler in terms of administrative and logistic workload.A survey was conducted in 10 European countries. Members of the European Clinical Research Infrastructures Network working party number 1, with expertise in the field of ethics, responded