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 g ×4 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 (0-240 min) of pain intensity (Numerical Scale) after thermal pain stimulation using Pathway-Medoc

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