Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamol ('Migraleve') in tablet and suppository form in rats.

Studies in rats were carried out to determine the acute toxicity and analgesic effect of a combination preparation ('Migraleve') containing codeine and paracetamol and the individual analgesics when given orally or by rectal administration. The results showed that the combination was no more toxic than paracetamol alone and, on the basis of the LD50:ED50 ratio, was less toxic by the oral than by the rectal route. In the rat-tail test, the combination induced a well-defined dose-dependent analgesic response which was greater after rectal administration. Codeine and paracetamol tested individually were effective only at relatively high dosage and, like the combination, their analgesic effects were greater after rectal administration and more clearly dose-dependent than after oral administration. Comparison of the area under the time-effect curves for the combination and the individual components confirmed the synergism between codeine and paracetamol.