Antipyrine - new light on an old drug.

The time courses of analgesic activity of 4 different tablets containing different amounts of antipyrine were determined in 14 volunteers using electrical tooth pulp stimulation to elicit pain. Drug action was monitored by following somatosensory evoked potentials obtained from electroencephalographic measurements as well as pain rating and pain threshold determination. The results were compared with data obtained after administration of 1000 mg acetaminophen and two different doses of aspirin (500 and 1000 mg). At the same time drug concentration in saliva of the same volunteers was analyzed by quantitative in situ thin-layer-chromatography to investigate the pharmacokinetics. Furthermore, the in vitro drug release from the different tablets was studied with a continuous flow cell model. Antipyrine produced reliable analgesic activity. The onset of action was significantly faster than after administration of the same dose of aspirin, and the effect lasted longer than after intake of the same dose of acetaminophen. Comparison of the drug action and drug level in the body showed an excellent correlation between pharmacodynamics and pharmacokinetics. The study confirms our earlier findings on the value of somatosensory evoked potentials as a method to investigate the pharmacodynamics of weak analgesics in humans. The results also suggest to reconsider the use of antipyrine as an over-the-counter analgesic.