Bioavailability of intranasal formulations of dihydroergotamine.
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%.


CONCLUSIONS
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.
van der Kuy
P H
PH
Department of Pharmacy, Laurentius Hospital, Roermond, The Netherlands. H.vanderKuy@lzr.nl
Lohman
J J
JJ
Hooymans
P M
PM
Ter Berg
J W
JW
Merkus
F W
FW
D000042:Absorption; D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000008:administration & dosage; D004087:Dihydroergotamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011208:Powders; D012016:Reference Values; D013810:Therapeutic Equivalency; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins
D000336:Aerosols; D003505:Cyclodextrins; D004338:Drug Combinations; D011208:Powders; D014662:Vasoconstrictor Agents; D047392:beta-Cyclodextrins; D004087:Dihydroergotamine; C031215:betadex