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.