ISSN:
1432-1041
Keywords:
Key words Dihydroergotamine
;
Absorption
;
Intranasal
;
Randomly methylated β-cyclodextrin (RAMEB)
;
Pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract 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 β-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 μl); 2 mg DHEM/4 mg RAMEB nasal powder; 2 mg Diergo nasal spray ( =four puffs of 125 μl); 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050692
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