Human pharmacokinetics of dihydroergotamine administered by nasal spray

Humbert, Henri; Cabiac, M. D.; Dubray, Claude; Lavene, D.

doi:10.1016/s0009-9236(96)90053-3

Cited by 45 publications

(49 citation statements)

References 14 publications

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“…In humans, the differences in C max , T max , and bioavailability between nasal DHE sprays with or without caffeine were also nonsignificant. 5 When the amount of RAMEB in liquid sprays was decreased, the intranasal bioavailability of DHE did not change substantially. Nevertheless, by adding RAMEB to liquids it is possible to dissolve higher amounts of DHEM, which will result in more concentrated formulations.…”

Section: Discussionmentioning

confidence: 98%

“…However, in humans, a decrease in nasal DHE absorption was observed for large volumes of spray, which was probably due to spilling of the liquid from the nasal cavity. 5 Another difference between the commercial preparations and the investigational liquid A was the excipient used for isotonicity. Liquid A contained mannitol, but the commercial nasal sprays G and H contained glucose.…”

Section: Discussionmentioning

confidence: 99%

“…DHE nasal spray was found to be safe and significantly superior to a placebo for the treatment of acute headache pain and nausea associated with common or classic migraine. [2][3][4] The bioavailability of DHE in humans following nasal administration was 38.4% relative to that following intramuscular injection, and the kinetics showed linear dose proportionality in the dose range of 1 to 4 mg. 5 The DHE nasal spray that is currently on the market consists of an ampule with DHEM at 4 mg/mL, caffeine, and glucose and is administered in a dose of 0.5 mg per puff (0.125 mL). 5 The ampule has to be placed into a nebulizer when the migraine attack occurs, and after it has been opened, it has to be used within 24 h. The limited stability of the nasal formulation and the requirement to prepare the device at the time of the attack are drawbacks of this nasal spray.…”

Section: Introductionmentioning

confidence: 99%

“…This regimen is recommended to avoid spillage of the solution from the nose. 5 The aim of the present study was to develop a pharmaceutically more stable formulation of DHE that can be prepared at higher drug concentrations to administer a similar intranasal dose of DHE in a much smaller spray volume. To increase the solubility of DHE, randomly methylated -cyclodextrin (RAMEB) was used.…”

Section: Introductionmentioning

confidence: 99%

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Nasal Absorption of Dihydroergotamine from Liquid and Powder Formulations in Rabbits

Marttin¹,

Romeijn²,

Verhoef³

et al. 1997

Journal of Pharmaceutical Sciences

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Nasal drug delivery is an interesting route of administration for dihydroergotamine in migraine therapy. The currently available formulation contains dihydroergotamine at 4 mg/mL. For a nasal dose of 2 mg, a volume of 0.5 mL has to be administered, which sometimes leads to spillage of the formulation. The aim of the present study was to develop a nasal spray with a dihydroergotamine concentration of 10 mg/mL. To increase the solubility and stability of dihydroergotamine, randomly methylated beta-cyclodextrin was used. Liquid formulations and lyophilized powders of dihydroergotamine and randomly methylated beta-cyclodextrin were prepared. The liquid and powder formulations were compared by determining their pharmacokinetics and absolute bioavailability after nasal administration in rabbits. Nasal sprays were significantly more effective than drops in increasing the nasal bioavailability of dihydroergotamine, but the amount of randomly methylated beta-cyclodextrin in liquid sprays did not significantly alter the nasal absorption. For powder formulations, the dihydroergotamine absorption was dependent on the amount of methylated beta-cyclodextrin and powder volume, and the nasal bioavailability from the optimal powder was slightly, but not significantly, higher than that for liquids. In conclusion, the formulations investigated are a substantial improvement of the current commercial formulation, not only because the spray volume of the liquid spray can be reduced 2.5 times, but also because of the increased stability of liquid and powder sprays with randomly methylated-beta-cyclodextrin.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nasal Absorption of Dihydroergotamine from Liquid and Powder Formulations in Rabbits

Marttin¹,

Romeijn²,

Verhoef³

et al. 1997

Journal of Pharmaceutical Sciences

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show abstract

“…The volume of the nasal cavity and the total surface area of the nasal epithelium in human are 16-18 ml and 180 cm 2 , respectively. [17][18][19][20][21] Those in the rat are 0.4 ml and 10 cm 2 , which are 2-5% of the human. In most human studies, the volume instilled to the nasal cavity was 50-200 ml.…”

Section: Methodsmentioning

confidence: 99%