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Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex
V Piguet1, J Desmeules, P Dayer
1Division of Clinical Pharmacology and Pain Center, University Hospital, Geneva, Switzerland.
Objective:
The analgesic efficacy of intravenous doses of acetaminophen (paracetamol) 0.5 g, 1 g and 2 g (administered as propacetamol) was assessed in 11 healthy subjects in a randomised, double-blind, placebo-controlled crossover study. The antinociceptive effect was assessed over 8 h by measurement of the nociceptive flexion reflex threshold (R-III) in response to selective transcutaneous electrical stimulations.
Results:
After acetaminophen 0.5 g, R-III increased to a mean maximum of 23% over baseline values; after 1 g to 28%, and after 2 g to 40%. The AUC(0-8 h) of the analgesic effects and the AUC(0-8 h) of plasma concentrations closely correlated and were dose-dependent: rs = 0.37, for R-III and rs = 0.94, for the plasma concentrations. Intravenous acetaminophen exerted a dose-dependent central antinociceptive effect.
