Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines

Lionetto, Luana; Casolla, Barbara; Mastropietri, Fabiola; D'Alonzo, Lidia; Negro, Andrea; Simmaco, Maurizio; Martelletti, Paolo

doi:10.1517/17425255.2012.701618

Cited by 15 publications

(9 citation statements)

References 46 publications

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“…Absorption was substantially faster than for orally administered zolmitriptan, with less measurable N-desmethyl zolmitriptan metabolite, presumably due to a lack of first pass metabolism. PK parameters for subcutaneous sumatriptan and oral zolmitritpan in this study were similar to those previously reported [14,15].…”

Section: Conclusion and Discussionsupporting

confidence: 90%

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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Section: Conclusion and Discussionsupporting

confidence: 90%

Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Kellerman¹,

Ameri²,

Tepper

2017

Pain Manag.

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“…Firstly, triptans attenuated the release of vasoactive peptides trigeminal system, as well as reduced the migraine vascular inflammation. Moreover, triptans were shown to potentially inhibit the nociceptive pathway of central sensitization, thus helped to relieve the pain from migraine [103, 104]. …”

Section: Discussionmentioning

confidence: 99%

Network meta-analysis of migraine disorder treatment by NSAIDs and triptans

Han

Wang

et al. 2016

J Headache Pain

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BackgroundMigraine is a neurological disorder resulting in large socioeconomic burden. This network meta-analysis (NMA) is designed to compare the relative efficacy and tolerability of non-steroidal anti-inflammatory agents (NSAIDs) and triptans.MethodsWe conducted systematic searches in database PubMed and Embase. Treatment effectiveness was compared by synthesizing direct and indirect evidences using NMA. The surface under curve ranking area (SUCRA) was created to rank those interventions.ResultsEletriptan and rizatriptan are superior to sumatriptan, zolmitriptan, almotriptan, ibuprofen and aspirin with respect to pain-relief. When analyzing 2 h-nausea-absence, rizatriptan has a better efficacy than sumatriptan, while other treatments indicate no distinctive difference compared with placebo. Furthermore, sumatriptan demonstrates a higher incidence of all-adverse-event compared with diclofenac-potassium, ibuprofen and almotriptan.ConclusionThis study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-016-0703-0) contains supplementary material, which is available to authorized users.

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“…This implies that the efficacy of triptans in prevention of migraine depends on their concentrations. Considering that frovatriptan has a long half-life (26 h [33]) and zolmitriptan posses a short half-life (3 h [38]), the frequency and dose should be adjusted when a triptan is used in the prevention of MM.…”

Section: Discussionmentioning

confidence: 99%

Triptans in prevention of menstrual migraine: a systematic review with meta-analysis

Guan

Fan

et al. 2013

J Headache Pain

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Randomized clinical trials (RCT) assessing the efficacy and tolerability of triptans compared with placebo as short-term prophylaxis of menstrual migraine (MM) were systematically reviewed in this study. Triptans, which interfere with the pathogenesis of migraine and are effective in relieving associated neurovegetative symptoms, have been extensively proposed for prevention of menstrual migraine attacks. We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized, double-blind, placebo-controlled trials on triptans for MM until 1 Oct, 2012. A total of six RCTs were identified. Two authors independently assessed trial’s quality and extracted data. Numbers of participants free from MM per perimenstrual period (PMP), requiring rescue medication, suffering from headache-associated symptoms and experiencing adverse events in treatment and control groups were used to calculate relative risk (RR) and number needed to treat (NNT) with their corresponding 95% confidence interval (CI). A total of 633 participants received frovatriptan 2.5 mg QD, 584 received frovatriptan 2.5 mg BID, 392 received naratriptan 1 mg BID, 70 received naratriptan 2.5 mg BID, 80 received zolmitriptan 2.5 mg BID, 83 received zolmitriptan 2.5 mg TID and 1104 received placebo. Overall, triptans is an effective, short-term, prophylactic treatment of choice for MM. Considering MM frequency, severity and adverse events, frovatriptan 2.5 mg BID and zolmitriptan 2.5 mg TID tend to be the preferred regimens.

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Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines

Cited by 15 publications

References 46 publications

Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray

Network meta-analysis of migraine disorder treatment by NSAIDs and triptans

Triptans in prevention of menstrual migraine: a systematic review with meta-analysis

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