Inhaled drug therapy development for the treatment of migraine

ABSTRACT

Introduction: The inhalation of substances, both medicinally and recreationally, is a commonly used method of drug administration but has been underutilized in the treatment of neurologic disorders such as migraine. Three drugs have been studied as potential inhalable treatments for acute migraine: dihydroergotamine (MAP0004), prochlorperazine (Staccato prochlorperazine), and loxapine (Staccato loxapine).

Areas covered: This review discusses the available literature describing the pharmacokinetics, tolerability and efficacy of MAP0004, Staccato prochlorperazine and Staccato loxapine, including data from Phase II and Phase III clinical trials.

Expert opinion: Inhaled DHE offers rapid absorption with a pharmacokinetic profile similar to IV administration. Improved side effect profile results from more selective binding at antimigraine serotonergic receptors 5-HT_1B and 5-HT_1D. Inhaled prochlorperazine is rapidly absorbed and resulted in statistically significant migraine pain relief at 2 hours compared to placebo but is not currently being pursued by the manufacturer as a potential migraine abortive. Inhaled loxapine is also rapidly absorbed into systemic circulation but Phase IIb trials did not show statistically improved pain relief or pain freedom compared to placebo. MAP0004 will likely provide a good alternative to patients seeking rapid relief without the need for injection or other invasive routes.

KEYWORDS:

• Aerosols
• efficacy
• dihydroergotamine
• inhaled
• loxapine
• migraine
• prochlorperazine
• pulmonary
• tolerability

Article highlights

• Limitations of current abortive treatments for migraine include: unreliable pharmacokinetics, poor bioavailability, extensive first-pass metabolism, injection site pain, inconvenience of use and patient avoidance of self-injection.

• Due to its anatomy, the lungs are an excellent portal for aerosolized medications intended for systemic absorption.

• Three drugs have been studied as potential inhalable treatments for acute migraine: dihydroergotamine, prochlorperazine and loxapine.

• Inhaled DHE offers rapid absorption with a pharmacokinetic profile similar to IV administration.

• Inhaled prochlorperazine and loxapine have shown potential advantage over placebo, although not statistically significant in the case of loxapine.

This box summarizes key points contained in the article.

Declaration of interest

S Silberstein has received honoraria for his role as a consultant and/or advisory panel member for: Alder Biopharmaceuticals; Allergan, Inc.; Amgen; Avanir Pharmaceuticals, Inc.; Curelator, Inc.; Depomed; Dr. Reddy’s Laboratories; eNeura Inc.; electroCore Medical, LLC; Lilly USA, LLC; Supernus Pharmaceuticals, Inc.; Teva Pharmaceuticals, and Trigemina, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.