Abstract Details

Title Pharmacokinetics, safety, and tolerability of DFN-02, an intranasal sumatriptan spray containing a permeation enhancer, compared with intranasal sumatriptan in healthy adults

Topic Headache

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-005

Objective

To compare the pharmacokinetic characteristics of intranasal commercial sumatriptan (Imitrex^®) 20 mg in healthy adults, with DFN-02, a novel intranasal product comprised of sumatriptan 10 mg plus 0.20% permeation enhancer, 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM, Intravail^® A3).

Background Intranasal sumatriptan (Imitrex^®) may be an alternative for patients who refuse injections and cannot tolerate oral agents, but low bioavailability and slow absorption limit the clinical utility of the currently marketed formulation, highlighting an unmet need for an effective, non-oral migraine medication with a rapid onset of action. To overcome the slow absorption profile associated with intranasal administration, we evaluated the impact of 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM, Intravail^® A3) a permeation enhancer, on sumatriptan's pharmacokinetic profile.

Design/Methods An open-label, randomized, single-dose, three-way crossover bioavailability study was conducted comparing a single intranasal formulation of DFN-02 delivered via monodose and multidose devices with a single dose of intranasal sumatriptan 20 mg (Imitrex) in 18 healthy, fasted adults. Subjects received a single dose of each treatment with at least three days between treatments. Blood was sampled for pharmacokinetic evaluation of sumatriptan and DDM through 24 hours postdose; safety and tolerability were monitored throughout the study.

Results

Absorption was markedly faster with the DFN-02 monodose and multidose devices than with intranasal Imitrex 20 mg: t_max was 15 minutes for DFN-02 monodose, 10 minutes for DFN-02 multidose, and 2 hours for intranasal Imitrex 20 mg. C_max and AUC_0-2 were significantly higher for DFN-02 than for intranasal Imitrex 20 mg, but AUC_0-∞ values were similar.

Conclusions

With DFN-02, plasma sumatriptan peaked much earlier than intranasal Imitrex 20 mg. Systemic exposure to the DFN-02 excipient DDM was short-lived. The safety and tolerability of DFN-02 appear to be comparable to intranasal sumatriptan. Addition of a permeation enhancer improved the absorption profile markedly compared with intranasal Imitrex.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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