Bioavailability of intranasal formulations of dihydroergotamine

Objective: A comparison of the pharmacokinetic properties of two novel intr anasal preparations of dihydroergotamine mesilate (DHEM) with a commerciall y available intranasal preparation. Methods: Two intranasal formulations of DHEM in combination with randomly m ethylated beta-cyclodextrin (RAMEB) were prepared. Subsequently, in an open , randomised, crossover study in nine healthy volunteers, the following med ication was administered: 2 mg DHEM/2% RAMEB nasal spray (= two puffs of 10 0 mu l); 2 mg DHEM/4 mg RAMEB nasal powder; 2 mg Diergo nasal spray (= four puffs of 125 mu l); 0.5 mg DHEM i.m., and 2 mg DHEM solution p.o. Results: No statistically significant differences were found in maximum pla sma concentration (C-max), time to reach C-max (t(max)), area under plasma concentration-time curve (AUC(0-8 h)), Frel((t=8 h)) and C-max/AUC((t=8 h)) for the three intranasal preparations. The relative bioavailabilities of t he DHEM/RAMEB nasal spray, the DHEM/RAMEB nasal powder and the commercially available DHEM nasal spray were 25%, 19% and 21%, respectively, in compari son with i.m. administration. The relative bioavailability after oral admin istration was 8%. Conclusion: The pharmacokinetic properties of the novel intranasal preparat ions are not significantly different from the commercially available nasal spray. Advantages of the DHEM/RAMEB nasal spray are (1) less complicated ha ndling, (2) reduction of the number of puffs and (3) a preference by the vo lunteers.