Double-blind, placebo controlled comparison of paracetamol and paracetamol plus codeine--a quantitative evaluation by...

The aim of the present double-blind, placebo controlled, three-way cross over study was to evaluate the analgesic efficacy of single oral doses of paracetamol 1.0 g and paracetamol 1.0 g plus codeine 60 mg. Pain threshold and brain evoked potentials to laser stimulation were determined hourly for 6 h in 12 healthy volunteers. Pain threshold was significantly elevated compared to placebo 1 and 2 h after paracetamol ingestion. Paracetamol 1.0 g plus codeine 60 mg was superior to placebo 1 to 6 h after medication. Only at 1 and 2 h after ingestion the combined drug was better than paracetamol. The evoked potentials were significantly depressed compared to placebo 2 and 4 h after paracetamol. The combination of paracetamol and codeine was superior to placebo 1 to 6 h after ingestion. The potentials showed no difference between the two active drugs. The total analgesic effect (approximation of area under the time-efficacy curve), showed that the combined drug was superior to plain paracetamol. A higher incidence of adverse effects in 10 of the 12 subjects was observed after ingestion of the combined drug compared to plain paracetamol (1 of 12). Paracetamol appears to exert part of its action by a central effect. There was at least 1 h between the peak plasma concentration of paracetamol and the peak hypoalgesia.