Absorption kinetics of dihydroergotoxine following oral administration to man

The absorption characteristics of dihydroergotoxine administered as an oral solution, tablet and retard capsule have been determined in a randomised cross-over investigation in 12 healthy males. The plasma concentrations of dihydroergotoxine produced by the three preparations, measured using a specific and sensitive radioimmuno-assay method over 24 h, exceeded 200 pg ml-1 for approximately 5 h and decayed in a biphasic manner with a slowest measured half-life of 12-14 h. The retard capsule differs from the other two preparations in having a low Cmax (50% of that recorded for the solution) and a clearly defined plateau. The bioavailability of the retard capsule was similar to that for the solution indicating that first-pass metabolism is not significantly increased following a three-fold prolongation in the absorption rate constant. The 20-40% greater bioavailability of dihydroergotoxine solution and retard capsule in comparison with the standard tablet may be due to a reduced contact time with gastric secretions achieved by means of rapid absorption from the stomach (solution) or delayed release at pH 1.5 (retard capsule).