Bioavailability of slow-release co-dergocrine mesylate (dihydroergotoxine) formulations

The relative bioavailability and plasma concentration profile of dihydroergotoxine as a solution, standard tablets and slow-release formulations have been compared in 12 healthy subjects following the application of 4-5 mg as a single dose or as 2-3 smaller dose units given at 5 h intervals. Plasma dihydroergotoxine concentrations were measured using a sensitive and highly specific radioimmunoassay procedure. The plasma concentration profile after a single 4.5 mg SR-capsule with relative bioavailability 92% (Oral solution, 4.5 mg as single dose = 100%), releasing 80% of the capsule contents within 8 h, was similar to that achieved following the application of 2-3 divided doses at 5 h intervals of a solution (relative bioavailability = 85%), standard tablet (relative bioavailability = 99%) or SR-tablets (relative bioavailability 78%). Slow-release formulations of dihydroergotoxine do not lead to high postdose concentrations as seen with solutions and standard tablets. Application of a single 4.5 mg SR-capsule can maintain prolonged plateau concentrations exceeding 100 pg/ml over 10 h. Reducing the rate of presentation of dihydroergotoxine to the body in the form of slow release formulations or by using spaced doses does not markedly affect bioavailability when compared to a solution.