Non-oral formulations of triptans and their use in acute migraine

Dahlöf, Carl

doi:10.1007/s11916-005-0064-x

Cited by 19 publications

(10 citation statements)

References 61 publications

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“…For moderate-to-severe migraine, treatment guidelines recommend the first-line use of triptans [2][3][4]. Optimal migraine treatment provides rapid pain relief with good palatability; currently available formulations and routes of administration for migraine medications do not fully meet these criteria.Although orally administered medications are user-friendly, they have some drawbacks [5]. Drug absorption is typically not rapid and may be further hindered by gastrointestinal dysmotility, resulting in inconsistent treatment effects.…”

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confidence: 99%

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Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Kellerman¹,

Ameri²,

Tepper

2017

Pain Manag.

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Adhesive Dermally-Applied Microarray (ADAM) is a device for intracutaneous drug administration consisting of a 3 cm 2 disposable array of drug-coated titanium microprojections on an adhesive backing. It is applied using a low cost, reusable, handheld applicator. Microprojections penetrate the stratum corneum, delivering drug proximal to capillaries with limited likelihood of pain. The pharmacokinetics of zolmitriptan delivery using ADAM was evaluated in 20 healthy volunteers. Median t max was <20 min, comparable to subcutaneous sumatriptan. Absorption was faster than for oral zolmitriptan, with higher exposure in the first 2 h. Most adverse events were consistent with those seen in previous triptan trials. Application site reactions were generally mild and resolved within 24 h. ADAM zolmitriptan shows a promising pharmacokinetic profile for migraine treatment. Migraine is a common cause of disability, and despite the availability of multiple treatment options, considerable unmet need persists [1]. For moderate-to-severe migraine, treatment guidelines recommend the first-line use of triptans [2][3][4]. Optimal migraine treatment provides rapid pain relief with good palatability; currently available formulations and routes of administration for migraine medications do not fully meet these criteria.Although orally administered medications are user-friendly, they have some drawbacks [5]. Drug absorption is typically not rapid and may be further hindered by gastrointestinal dysmotility, resulting in inconsistent treatment effects. Moreover, as many patients experience nausea and vomiting in association with migraine, they may experience difficulty in swallowing or retaining oral formulations. Delayed gastric emptying in migraine may be further exacerbated by triptans, which can prolong gastric emptying time by activating 5-HT1 receptors on gastric myenteric neurons [6][7][8]. Therefore, in many patients, rapidly acting nonoral formulations may be preferable.Available nonoral migraine medications include injectable and intranasal formulations of sumatriptan and zolmitriptan nasal spray. Among these, subcutaneously injected sumatriptan is most rapidly absorbed with a time to maximum concentration (t max ) of 10-12 min [9]. For sumatriptan nasal powder and nasal spray, the average t max are 45 min [10] and approximately 2 h [11], respectively. The t max for zolmitriptan nasal spray is 1.5-2.5 h [12]. While providing more rapid absorption than orally administered triptans, these formulations have limitations that include needle aversion and poor palatability of nasal formulations. Here we describe an investigational device that circumvents these limitations by providing intracutaneous delivery of zolmitriptan. The Adhesive Dermally-Applied MicroarrayThe Adhesive Dermally-Applied Microarray (ADAM) is an investigational product for intracutaneous drug delivery allowing rapid absorption into the bloodstream. It consists of a disposable adhesive backing, with an array of drug (zolmitriptan)-coated titanium microprojections m...

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mentioning

confidence: 99%

“…Although orally administered medications are user-friendly, they have some drawbacks [5]. Drug absorption is typically not rapid and may be further hindered by gastrointestinal dysmotility, resulting in inconsistent treatment effects.…”

mentioning

confidence: 99%

Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Kellerman¹,

Ameri²,

Tepper

2017

Pain Manag.

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“…A number of puzzling clinical observations have been made when triptans are used in the acute treatment of migraine headache. One of the more clinically important findings is that the reliability of response to a triptan when administered orally is undesirably low [61]. In general, oral therapy with triptan provides pain relief in some of the attacks, but the within-patient consistency of response for three of three attacks only occurs in approximately 40% of patients treated with a triptan tablet.…”

Section: Triptan Responders and Non-respondersmentioning

confidence: 99%

“…However, the gastrointestinal absorption of drugs administered orally may be significantly impaired during migraine attacks [69]. The most likely explanation is that the crucial gastrointestinal motility is inhibited and the gastric emptying time delayed during the migraine attack [61,67,[69][70][71][72][73]. In addition, there is always a risk that the migraine-induced nausea culminates in vomiting.…”

Section: Impaired Gastrointestinal Absorptionmentioning

confidence: 99%

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Cutaneous allodynia and migraine: Another view

Dahlöf¹

2006

Current Science Inc

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The paradigm of early treatment of the migraine attack at mild pain intensity has become one alternative to circumventing the problem of compromised oral absorption of symptomatic drugs due to migraine-induced gastrointestinal dysmotility. Early treatment also has been proposed to be advantageous because most migraineurs could be less responsive to delayed treatment, owing to the development of central sensitization of the trigeminal pain transmission. Ranking the underlying principles, it seems that the improved response to an oral triptan formulation at mild migraine symptom intensity has more to do with less impaired gastrointestinal absorption in the early stage of the attack than decreasing the time and preventing chances for central sensitization and development of cutaneous allodynia. Furthermore, parenteral administration of a triptan is always more likely to provide relief of symptoms than conventional tablets, even when it is used later in the course of the migraine attack. Individually tailored use of the available triptan formulations will increase, without any doubt, the within-migraineur consistency of response. It also will reduce the overall proportion of migraine attacks or migraineurs not responding to triptan treatment. Notwithstanding, the recommendation of early treatment during the migraine attack when the pain is mild remains valid.

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Tablets and Other Solid Dosage Forms for Systemic Oral Mucosal Drug Delivery

Rane¹,

Moe²

2015

Advances in Delivery Science and Technology

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Non-oral formulations of triptans and their use in acute migraine

Cited by 19 publications

References 61 publications

Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Cutaneous allodynia and migraine: Another view

Tablets and Other Solid Dosage Forms for Systemic Oral Mucosal Drug Delivery

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