Summary
Migraine is a common, multisymptom disorder that can severely impact the daily activities of migraineurs. Triptans (primarily sumatriptan) are the most commonly prescribed treatment for migraine and are considered a relatively safe and effective initial therapy. Unfortunately, current sumatriptan formulations (i.e., oral, nasal, subcutaneous) may be associated with limitations that can result in patients’ delaying or avoiding treatment. For oral formulations, these limitations include difficulty in taking an oral medication due to the nausea and vomiting that often accompany migraine, and inconsistent absorption, whereas nasal and subcutaneous formulations may be associated with low bioavailability and an undesirable rate of adverse events, respectively. An alternative to current formulations is transdermal drug delivery, particularly iontophoresis. Transdermal delivery has several advantages over current formulations, including avoidance of the gastrointestinal tract, controlled and sustained delivery, and convenient administration. This article reviews the in vitro, in vivo, and preclinical data supporting the use of iontophoresis for the delivery of sumatriptan, as well as the recent clinical data for Zelrix (NuPathe Inc., Conshohocken, PA), an iontophoretic sumatriptan patch currently in phase III development for the treatment of migraine.
Key Words: Iontophoresis, migraine, transdermal, sumatriptan, Zelrix
References
- 1.Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343–349. doi: 10.1212/01.wnl.0000252808.97649.21. [DOI] [PubMed] [Google Scholar]
- 2.Silberstein SD. Migraine symptoms: results of a survey of self-reported migraineurs. Headache. 1995;35:387–396. doi: 10.1111/j.1526-4610.1995.hed3507387.x. [DOI] [PubMed] [Google Scholar]
- 3.Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754–762. doi: 10.1212/wnl.55.6.754. [DOI] [PubMed] [Google Scholar]
- 4.Jhee SS, Shiovitz T, Crawford AW, Cutler NR. Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review. Clin Pharmacokinet. 2001;40:189–205. doi: 10.2165/00003088-200140030-00004. [DOI] [PubMed] [Google Scholar]
- 5.Siegel SJ, O’Neill C, Dube LM, et al. A unique iontophoretic patch for optimal transdermal delivery of sumatriptan. Pharm Res. 2007;24:1919–1926. doi: 10.1007/s11095-007-9317-1. [DOI] [PubMed] [Google Scholar]
- 6.GlaxoSmithKline. IMITREX (sumatriptan succinate) Tablets prescribing information. 2007.
- 7.GlaxoSmithKline. IMITREX (sumatriptan) Nasal spray prescribing information. 2007.
- 8.GlaxoSmithKline. IMITREX (sumatriptan succinate) Injection prescribing information. 2008.
- 9.Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv. 2006;13:175–187. doi: 10.1080/10717540500455975. [DOI] [PubMed] [Google Scholar]
- 10.Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26:1261–1268. doi: 10.1038/nbt.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Femenia-Font A, Balaguer-Femandez C, Merino V, Rodilla V, Lopez-Castellano A. Effect of chemical enhancers on the in vitro percutaneous absorption of sumatriptan succinate. Eur J Pharm Biopharm. 2005;61:50–55. doi: 10.1016/j.ejpb.2005.02.014. [DOI] [PubMed] [Google Scholar]
- 12.Femenia-Font A, Merino V, Rodilla V, Lopez-Castellano A. High-performance liquid Chromatographic determination of sumatriptan after in vitro transdermal diffusion studies. J Pharm Biomed Anal. 2005;37:621–626. doi: 10.1016/j.jpba.2004.11.029. [DOI] [PubMed] [Google Scholar]
- 13.Femenia-Font A, Padula C, Marra F, et al. Bioadhesive monolayer film for the in vitro transdermal delivery of sumatriptan. J Pharm Sci. 2006;95:1561–1569. doi: 10.1002/jps.20638. [DOI] [PubMed] [Google Scholar]
- 14.Balaguer-Femandez C, Femenia-Font A, Del Rio-Sancho S, Merino V, Lopez-Castellano A. Sumatriptan succinate transdermal delivery systems for the treatment of migraine. J Pharm Sci. 2008;97:2102–2109. doi: 10.1002/jps.21129. [DOI] [PubMed] [Google Scholar]
- 15.Femenia-Font A, Balaguer-Femandez C, Merino V, Lopez-Castellano A. Combination strategies for enhancing transdermal absorption of sumatriptan through skin. Int J Pharm. 2006;323:125–130. doi: 10.1016/j.ijpharm.2006.05.049. [DOI] [PubMed] [Google Scholar]
- 16.Femenia-Font A, Balaguer-Fernandez C, Merino V, Lopez-Castellano A. Iontophoretic transdermal delivery of sumatriptan: effect of current density and ionic strength. J Pharm Sci. 2005;94:2183–2186. doi: 10.1002/jps.20447. [DOI] [PubMed] [Google Scholar]
- 17.Patel SR, Zhong H, Sharma A, Kalia YN. In vitro and in vivo evaluation of the transdermal iontophoretic delivery of sumatriptan succinate. Eur J Pharm Biopharm. 2007;66:296–301. doi: 10.1016/j.ejpb.2006.11.001. [DOI] [PubMed] [Google Scholar]
- 18.Pierce M, Marbury T, O’Neill C, Siegel S, Du W, Sebree T. Zelrix: a novel transdermal formulation of sumatriptan. Headache. 2009;49:817–825. doi: 10.1111/j.1526-4610.2009.01437.x. [DOI] [PubMed] [Google Scholar]
- 19.Goldstein J, Pugach N, Smith T, Nett R, Angelov A, Pierce M. Acute anti-migraine efficacy and tolerability of Zelrix, a novel iontophoretic transdermal patch of sumatriptan. Cephalalgia. 2009;29(Suppl 1):20–20. [Google Scholar]
- 20.Garg T, Jain S, Singh HP, Sharma A, Tiwary AK. Elastic liposomal formulation for sustained delivery of antimigraine drug: in vitro characterization and biological evaluation. Drug Dev Ind Pharm. 2008;34:1100–1110. doi: 10.1080/03639040801965079. [DOI] [PubMed] [Google Scholar]
- 21.Patel SR, Zhong H, Sharma A, Kalia YN. Controlled non-invasive transdermal iontophoretic delivery of zolmitriptan hydrochloride in vitro and in vivo. Eur J Pharm Biopharm. 2009;72:304–309. doi: 10.1016/j.ejpb.2008.08.006. [DOI] [PubMed] [Google Scholar]