ZELRIX: a novel transdermal formulation of sumatriptan.
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| Title: | ZELRIX: a novel transdermal formulation of sumatriptan. |
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| Authors: | Pierce M (AUTHOR), Marbury T (AUTHOR), O'Neill C (AUTHOR), Siegel S (AUTHOR), Du W (AUTHOR), Sebree T (AUTHOR) |
| Source: | Headache: The Journal of Head & Face Pain. Jun2009, Vol. 49 Issue 6, p817-825. 9p. |
| Abstract: | Objective.- This study evaluated the pharmacokinetic and tolerability profiles of Zelrix[TM] (NuPathe Inc., Conshohocken, PA, USA), the novel formulation of sumatriptan (formerly known as NP101). Background.- Migraine is an episodic headache disorder characterized by a combination of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal disturbances, including nausea, vomiting, and gastric stasis are common and can result in significant impact on treatment. Triptans are 5-hydroxytriptanime1B/1D agonists that work on the trigeminal nerve that is activated during migraine. All triptans approved for use in the US are currently available as oral formulations; however, this may not be the ideal route of administration for many migraineurs. Sumatriptan is also available as a nasal spray and subcutaneous (sc) injection. Therefore, the need to develop improved methods for noninvasive parenteral delivery of triptans remains high. Methods.- This was a Phase I, single-center, open-label, crossover study that assessed the pharmacokinetic properties of a single dose of sumatriptan delivered using an iontophoretic transdermal patch in comparison with oral, injection, and nasal delivery. Subjects were healthy male and female volunteers who received each of 5 treatments: sumatriptan 100 mg oral tablets, sumatriptan 6 mg sc, sumatriptan 20 mg nasal spray, Zelrix I (transdermal patch with 3 g of gel solution delivering 6 mg of sumatriptan transdermally), or Zelrix II (transdermal patch containing 2.6 g of gel solution delivering 6 mg of sumatriptan). Results.- The Cmax for Zelrix was reduced to 30% and 28% of the sumatriptan sc dose, thereby reducing the risk of triptan-like sensations associated with high peak plasma concentrations. Plasma concentrations for Zelrix I and Zelrix II were intermediate between those for oral and nasal sumatriptan doses tested. Transdermal patch delivery of sumatriptan to the systemic circulation reached plasma concentrations of 10 ng/mL within about 30 minutes. The mean drug delivery of Zelrix I and II was 6.11 mg (confidence intervals [CI] 5.33-6.88) and 6.09 mg (CI 5.52-6.66), respectively. The AUC0-inf was approximately 99% for the Zelrix I patch and 100% for the Zelrix II patch as compared with sumatriptan 6 mg sc dose. Both doses of sumatriptan transdermal patches were well tolerated. Skin reactions at the patch site were mild and erythema resolved in most subjects within 48-72 hours. Conclusions.- The results from this study show that sumatriptan administration using a novel iontophoretic transdermal technology delivers plasma levels within the range for nasal spray, tablet, and injectable sumatriptan. Zelrix I and II were well tolerated and adverse events were mild and transient. Transdermal delivery of sumatriptan using the SmartRelief iontophoretic technology may prove beneficial for a large segment of the migraine population based upon fast, consistent delivery of drug and avoidance of common gastrointestinal disturbances associated with migraine. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| Abstract: | Objective.- This study evaluated the pharmacokinetic and tolerability profiles of Zelrix[TM] (NuPathe Inc., Conshohocken, PA, USA), the novel formulation of sumatriptan (formerly known as NP101). Background.- Migraine is an episodic headache disorder characterized by a combination of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal disturbances, including nausea, vomiting, and gastric stasis are common and can result in significant impact on treatment. Triptans are 5-hydroxytriptanime1B/1D agonists that work on the trigeminal nerve that is activated during migraine. All triptans approved for use in the US are currently available as oral formulations; however, this may not be the ideal route of administration for many migraineurs. Sumatriptan is also available as a nasal spray and subcutaneous (sc) injection. Therefore, the need to develop improved methods for noninvasive parenteral delivery of triptans remains high. Methods.- This was a Phase I, single-center, open-label, crossover study that assessed the pharmacokinetic properties of a single dose of sumatriptan delivered using an iontophoretic transdermal patch in comparison with oral, injection, and nasal delivery. Subjects were healthy male and female volunteers who received each of 5 treatments: sumatriptan 100 mg oral tablets, sumatriptan 6 mg sc, sumatriptan 20 mg nasal spray, Zelrix I (transdermal patch with 3 g of gel solution delivering 6 mg of sumatriptan transdermally), or Zelrix II (transdermal patch containing 2.6 g of gel solution delivering 6 mg of sumatriptan). Results.- The Cmax for Zelrix was reduced to 30% and 28% of the sumatriptan sc dose, thereby reducing the risk of triptan-like sensations associated with high peak plasma concentrations. Plasma concentrations for Zelrix I and Zelrix II were intermediate between those for oral and nasal sumatriptan doses tested. Transdermal patch delivery of sumatriptan to the systemic circulation reached plasma concentrations of 10 ng/mL within about 30 minutes. The mean drug delivery of Zelrix I and II was 6.11 mg (confidence intervals [CI] 5.33-6.88) and 6.09 mg (CI 5.52-6.66), respectively. The AUC0-inf was approximately 99% for the Zelrix I patch and 100% for the Zelrix II patch as compared with sumatriptan 6 mg sc dose. Both doses of sumatriptan transdermal patches were well tolerated. Skin reactions at the patch site were mild and erythema resolved in most subjects within 48-72 hours. Conclusions.- The results from this study show that sumatriptan administration using a novel iontophoretic transdermal technology delivers plasma levels within the range for nasal spray, tablet, and injectable sumatriptan. Zelrix I and II were well tolerated and adverse events were mild and transient. Transdermal delivery of sumatriptan using the SmartRelief iontophoretic technology may prove beneficial for a large segment of the migraine population based upon fast, consistent delivery of drug and avoidance of common gastrointestinal disturbances associated with migraine. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00178748 |
| DOI: | 10.1111/j.1526-4610.2009.01437.x |
