Rapid Oral Transmucosal Absorption of Sumatriptan, and Pharmacodynamics in Acute Migraine

Authors

  • Enrique Dilone,

    1. From the Novadel Pharma – Clinical Research, Flemington, NJ, USA (E. Dilone and M. Nedumpara); Novadel Pharma – Product Development, Flemington, NJ, USA (D. Bergstrom); NDS International Inc. – Clinical Pharmacology, Biglerville, PA, USA (B. Cabana); EBD Group, Carlsbad, CA, USA (A. W. Fox).
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  • David Bergstrom,

    1. From the Novadel Pharma – Clinical Research, Flemington, NJ, USA (E. Dilone and M. Nedumpara); Novadel Pharma – Product Development, Flemington, NJ, USA (D. Bergstrom); NDS International Inc. – Clinical Pharmacology, Biglerville, PA, USA (B. Cabana); EBD Group, Carlsbad, CA, USA (A. W. Fox).
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  • Bernard Cabana,

    1. From the Novadel Pharma – Clinical Research, Flemington, NJ, USA (E. Dilone and M. Nedumpara); Novadel Pharma – Product Development, Flemington, NJ, USA (D. Bergstrom); NDS International Inc. – Clinical Pharmacology, Biglerville, PA, USA (B. Cabana); EBD Group, Carlsbad, CA, USA (A. W. Fox).
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  • Mercy Nedumpara,

    1. From the Novadel Pharma – Clinical Research, Flemington, NJ, USA (E. Dilone and M. Nedumpara); Novadel Pharma – Product Development, Flemington, NJ, USA (D. Bergstrom); NDS International Inc. – Clinical Pharmacology, Biglerville, PA, USA (B. Cabana); EBD Group, Carlsbad, CA, USA (A. W. Fox).
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  • Anthony W. Fox,

    1. From the Novadel Pharma – Clinical Research, Flemington, NJ, USA (E. Dilone and M. Nedumpara); Novadel Pharma – Product Development, Flemington, NJ, USA (D. Bergstrom); NDS International Inc. – Clinical Pharmacology, Biglerville, PA, USA (B. Cabana); EBD Group, Carlsbad, CA, USA (A. W. Fox).
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  • the Sumatriptan Lingual Spray Study Group

    1. From the Novadel Pharma – Clinical Research, Flemington, NJ, USA (E. Dilone and M. Nedumpara); Novadel Pharma – Product Development, Flemington, NJ, USA (D. Bergstrom); NDS International Inc. – Clinical Pharmacology, Biglerville, PA, USA (B. Cabana); EBD Group, Carlsbad, CA, USA (A. W. Fox).
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  • Conflict of Interest: All of the authors are either employees or consultants to Novadel Pharma Inc., Flemington, NJ, the sponsor of this pair of clinical trials.

A. W. Fox, EBD Group, 2032 Corte del Nogal, Suite 120, Carlsbad, CA 92011, USA.

Abstract

Objectives.— (1) To determine whether sumatriptan can be absorbed across the oral mucosa, and, if so; then (2) to describe its pharmacokinetics; and (3) to investigate whether there are pharmacodynamic correlates of such pharmacokinetics in patients experiencing migraine attacks.

Methods.— Two clinical trials. The first, in normal volunteers, compared the pharmacokinetic performance of a lingual spray (LS) formulation of sumatriptan (2 dose sizes, one of which in both the fed and fasted state) with an orthodox 50-mg sumatriptan tablet. The second clinical trial, in a patient population enriched by documenting suboptimal response to an initial 50-mg sumatriptan tablet, was a multiple-attack, crossover, fixed dose-order, open-label comparison of sumatriptan administered by LS (up to 3 different dose sizes) and a 100-mg sumatriptan tablet.

Results.— The LS formulations resulted in double-peaked time-plasma concentration curves that are consistent with absorption of sumatriptan across the oral mucosa. The first Tmax was usually about 10-15 minutes. In the enriched patient population, this corresponded with evidence of earlier efficacy for the LS in comparison with a 50-mg tablet; the lower dose size for the former was consistent with oral mucosal drug absorption, and evasion of first-pass metabolism.

Conclusions.— The initial pharmacokinetics of LS approximate to those of a subcutaneous injection, albeit some fraction of these doses is also swallowed. These pharmacokinetics correspond with earlier effectiveness of LS in comparison with a 50-mg sumatriptan tablet, and at lower dose, in an enriched, relevant patient population. These initial studies support further development of this innovative formulation of sumatriptan and this new route of administration.

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