Assessment of the consistency of absorption of dihydroergotamine following oral inhalation: pooled results from four clinical studies.

Abstract

BACKGROUND:

MAP0004 is an investigational orally inhaled dihydroergotamine (DHE) delivered via a TEMPO(®) metered dose inhaler that was effective in the acute treatment of migraine in a large Phase 3 trial. Rapid and consistent absorption of DHE is important for efficacy in the acute treatment of migraine.

METHODS:

The pharmacokinetic parameters from four recent clinical studies, with doses including the proposed clinical dose of 1.0 mg nominal (0.65 mg emitted) MAP0004, were assessed for the consistency and speed of absorption of DHE.

RESULTS:

Across these studies, MAP0004 administration resulted in rapid DHE absorption, with a median time of maximum concentration (C(max)) of approximately 10 min. The C(max) and area under the curve from time zero to 2 hr associated with the MAP0004 1.0 mg nominal dose were also similar between the three studies with this dose. C(max) values after 1.0 mg MAP0004 administration were consistently lower than for 1.0 mg intravenous DHE administration, and C(max) appeared to correlate with incidence of nausea. In these studies, DHE absorption through the lung was fast, consistent, and not associated with any unique tolerability issues for this route of administration.

CONCLUSIONS:

These results provide evidence of the consistency of absorption that can be achieved with the use of an appropriate metered dose inhaler, which may translate into a predictable therapeutic response.

• Authors: Donald J Kellerman, Amy Forst, Daniel L Combs, Scott Borland, Shashidhar Kori
• Journal: Journal of aerosol medicine and pulmonary drug delivery (J Aerosol Med Pulm Drug Deliv) Vol. 26 Issue 5 Pg. 297-306 (Oct 2013) ISSN: 1941-2703 [Electronic] United States
• PMID: 23273242 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Vasoconstrictor Agents
• Dihydroergotamine

Topics

• Administration, Inhalation
• Adult
• Area Under Curve
• Clinical Trials as Topic
• Dihydroergotamine (administration & dosage, adverse effects, pharmacokinetics)
• Drug Delivery Systems
• Female
• Humans
• Lung (metabolism)
• Male
• Metered Dose Inhalers
• Vasoconstrictor Agents (administration & dosage, adverse effects, pharmacokinetics)