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Updated: Aug 2, 2026

Intranasal Administration of CNS Therapeutics to Awake Mice
Published on: April 8, 2013
Bioavailability of intranasal formulations of dihydroergotamine
P H van der Kuy1, J J Lohman, P M Hooymans
1Department of Pharmacy, Laurentius Hospital, Roermond, The Netherlands. H.vanderKuy@lzr.nl
Objective:
A comparison of the pharmacokinetic properties of two novel intranasal preparations of dihydroergotamine mesilate (DHEM) with a commercially available intranasal preparation.
Methods:
Two intranasal formulations of DHEM in combination with randomly methylated beta-cyclodextrin (RAMEB) were prepared. Subsequently, in an open, randomised, crossover study in nine healthy volunteers, the following medication was administered: 2 mg DHEM/2% RAMEB nasal spray (= two puffs of 100 microliters); 2 mg DHEM/4 mg RAMEB nasal powder; 2 mg Diergo nasal spray (= four puffs of 125 microliters); 0.5 mg DHEM i.m., and 2 mg DHEM solution p.o.
Results:
No statistically significant differences were found in maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under plasma concentration-time curve (AUC0-8 h), Frel(t = 8 h) and Cmax/AUC(t = 8 h) for the three intranasal preparations. The relative bioavailabilities of the DHEM/RAMEB nasal spray, the DHEM/RAMEB nasal powder and the commercially available DHEM nasal spray were 25%, 19% and 21%, respectively, in comparison with i.m. administration. The relative bioavailability after oral administration was 8%.
Conclusion:
The pharmacokinetic properties of the novel intranasal preparations are not significantly different from the commercially available nasal spray. Advantages of the DHEM/RAMEB nasal spray are (1) less complicated handling, (2) reduction of the number of puffs and (3) a preference by the volunteers.
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