Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex

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 rifler 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: r(s) = 0.37, for R-III and r(s) = 0.94, for the plasma concentrations. Intravenous acetaminophen exerted a dose-dependent central antinociceptive effect.