Interaction of dihydroergotamine and triacetyloleandomycin in the minipig

The kinetics of unchanged DHE and of the sum of parent drug and metabolites under the effect of acute TO exposure were investigated by comparing the areas under the plasma concentration-time curves after oral, intravenous and hepatoportal administration in minipigs. While TO (500 mg p.o. 15 min. before DHE) caused only a slight increase of plasma levels of parent drug or the sum of parent drug and metabolites after an intravenous dose of 1 mg DHE, there was an important and significant increase of the 0–24 hrs AUC’s after administration of (10 mg) oral or (1 mg) hepatoportal DHE. This finding strongly suggests that the interaction of TO and DHE occurs at the hepatic site.