Background: Chronic migraine may seem treatment-resistant when underlying medication-overuse headache (MOH) and psychosocial stressors are overlooked. This report describes a patient who was seen in a family medicine clinic with persistent triptan overuse and daily social stressors concealing the cause of her chronic headaches and highlights how pharmacologic and behavioral strategies restored control. Case presentation: A woman in her 40s with a 10-year history of migraine developed chronic daily headaches after years of near-daily eletriptan use. This persistent triptan overuse led to the failure of multiple preventive therapies during ongoing overuse. Symptom remission after eletriptan withdrawal confirmed the diagnosis of MOH. Subsequent stabilization with preventive treatment encouraging self-management and behavioral and physiotherapy interventions allowed her to achieve sustained remission and regain functional stability. Conclusions: This case demonstrates that unrecognized medication overuse, combined with stress and unrestricted access to triptans, can mimic treatment-resistant migraine. Chronic migraine can be managed and prevented through early screening for MOH, structured patient education, multidisciplinary management approaches, and strict regulation of OTC triptan dispensing.

Eletriptan hydrobromide (EHBr) exhibits poor oral bioavailability due to extensive first-pass metabolism by CYP3A4 and P-glycoprotein-mediated efflux at the blood-brain barrier. Therefore, this study was conceptualised to encapsulate EHBr into solid lipid nanoparticles (SLNs) and deliver them via a transdermal microneedle (MN) array for targeted brain delivery. SLNs were formulated using a lipid matrix comprising glyceryl monostearate, stearic acid and hydrogenated soy phosphatidylcholine, with Poloxamer-188 as the emulsifier. The optimised SLNs showed a particle size of 165.5 ± 71.75 nm, zeta potential of -27.1 ± 4.48 mV and entrapment efficiency of 63.25 ± 1.44%, and were incorporated into polymer-based MNs. The optimised MNs exhibited high drug content (93.65 ± 1.39%), good mechanical strength (p < 0.05), excellent insertion efficiency (F = 17.83, p = 3.03 × 10[-8]) and rapid in situ dissolution. Ex vivo studies demonstrated sustained EHBr release (89.67 ± 1.03% over 24 h), following first-order kinetics (R[2] = 0.998) with non-Fickian diffusion (n = 0.79). FTIR and XRD analyses confirmed drug excipient compatibility and formulation stability. In vivo evaluation in Wistar rats revealed significant antinociceptive, anxiolytic and anti-photophobic effects (p ≤ 0.027), and reduced neurogenic inflammation, confirming the enhanced brain delivery and bioavailability of EHBr.

A stability-indicating UHPLC-MS method was developed to investigate the stress degradation behavior of eletriptan hydrobromide under ICH-recommended acidic, alkaline, neutral, oxidative, thermal, and photolytic conditions. Significant degradation was observed only under acidic and oxidative stress. Four degradation products were isolated and structurally characterized using HRMS and NMR, including one novel dimeric species. The optimized UHPLC-MS method provided an 8-min runtime with good resolution, sensitivity, and suitability for routine analysis. These results offer the first complete structural insight into the degradation pathways of eletriptan hydrobromide. The study supports improved quality control and long-term stability assessment. The findings also bridge the knowledge gap left by earlier studies that reported unassigned degradation products. Three new degradation products were identified and isolated from oxidative degradation and a new degradation product isolated from the acid degradation, providing the first documented structural characterization of all four degradation products. Furthermore, we develop a UPLC MS method having 8-min runtime and good peak shape and resolution by using Acquity BEH C18 column (100 × 2.1 mm, 1.7 μm) column.

Limited information indicates that a maternal dose of eletriptan up to 80 mg daily produces low levels in milk and would not be expected to cause any adverse effects in breastfed infants.

Background/Objectives: Predicting whether a compound is subject to active transport is crucial in drug development. We propose a simple threshold for passive membrane permeability (Pm), derived from the cell's energy limitation, to identify compounds unlikely to be actively effluxed. Results: By considering fundamental cellular energy constraints, our approach provides a mechanistic rationale for why compounds with very high passive permeability in combination with low applied concentration will not undergo active efflux. This moves beyond the empirical observation (such as in previous systems that associate fast-permeating, poorly soluble compounds with low transporter activity) by grounding the prediction in the cell's energetic limitations. For MDCK (Madin-Darby canine kidney) cells, this threshold-normalized to the applied compound concentration (Cext)-was determined to be Pm×Cext = 10[-1.7] cm/s×µM. Methods: To derive this threshold, we conducted an extensive analysis of literature-reported efflux ratios (ERs) in MDCKII cells overexpressing efflux transporters (MDR1, BCRP, MRP2; 294 datapoints across 136 unique compounds). Concentration-dependent measurements for Amprenavir, Eletriptan, Loperamide, and Quinidine-chosen because these borderline compounds exhibited the highest Pm×Cext while still being actively effluxed-enabled the most accurate determination of the threshold. Literature ER values were re-evaluated through the experimental determination of reliable Pm values, as well as newly measured ER values with MDCK efflux assays. Conclusions: The results of these assays and the re-evaluation allowed us to reclassify all but three outliers (compounds with ER > 2.5 and log(Pm×Cext) > -1.7). In contrast, more than 60% of the compounds analyzed without significant ER values (123 compounds) fell above the threshold, in strong agreement with our theory of an energy limitation to active transport. This permeability threshold thus provides a simple and broadly applicable criterion to identify compounds for which active efflux is energetically not feasible and may serve as a practical tool for early drug discovery and optimization, pending further validation in practical applications.

Topological indices, derived from molecular graphs, provide valuable numerical descriptors for the comprehensive analysis of pharmaceuticals. These indices are pivotal in the physicochemical characterization and predictive assessment of various drugs. In this study, we calculate several degree-based topological indices for a range of migraine treatment medications, including aspirin, caffeine, eletriptan, ergotamine, sumatriptan, rizatriptan, verapamil, diclofenac, frovatriptan, and droperidol. The process involves several steps: data collection on the molecular structures of migraine drugs and their corresponding biological activities, followed by the calculation of descriptors that represent key features of molecules. Calculating the values of these descriptors, we use vertex degree, edge division, and the counting degree technique. We employ curvilinear regression models, including linear, quadratic, and cubic regressions, to analyze each topological indicator. This research emphasizes the application of curvilinear regression techniques and performs extensive testing using these models to enhance the understanding of drug properties. The Weighted Aggregated Sum Product Assessment (WASPAS) method is applied to evaluate and rank these drugs based on various topological indices attributes, integrating both the weighted sum model and the weighted product model to provide a comprehensive assessment.

Objective: Japan has resumed its health technology assessment to decide how to reduce high-cost drug prices. While drug price rules in Japan are comprehensive, they do not necessarily capture differences in product characteristics. This study examined the drug price revision strategy in Japan using migraine treatment with triptans as an example. Cost data from fiscal years (FY) 2018, 2020, and 2022 were utilized. Methods: A cost-utility analysis was conducted from the perspective of healthcare payers, focusing on Japanese patients aged over 18 years experiencing migraines. The study employed a base-case model with probabilities derived from a network meta-analysis. Direct costs included medical and drug costs. Effectiveness was assessed using the European Quality of Life 5-dimensions-3-level questionnaire. Deterministic and probabilistic sensitivity analyses were conducted to examine the level of uncertainty. Results: In FY2018, sumatriptan and eletriptan were cost-effective; however, the other triptans were dominated by sumatriptan. In FY2020, sumatriptan and eletriptan were cost-effective, and rizatriptan was extended-dominated; nevertheless, the other triptans were dominated by sumatriptan. In FY2022, naratriptan and eletriptan were cost-effective; however, the other triptans were dominated by naratriptan. The hierarchy of triptan strategies varied in each fiscal year. Conclusions: This study provides valuable insights into the drug price revision strategy in Japan. The variations could be problematic because in Japan, formulary management of triptans, for example, those for migraine, may face revaluation every other year. Discussions regarding this issue will be further explored in the future.

The triptans class of pharmaceuticals, which was created to treat acute migraine, is made up of indole-containing drugs that bind to a subset (1B/1D) of 5-hydroxytryptamine receptors and are agonists of serotonin receptors. At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists. Zolmitriptan, a synthetic tryptamine derivative and a well-known member of the triptan family, is available as an orally disintegrating tablet, nasal spray, and tablet. There are melt formulations of rizatriptan and zolmitriptan available on the market that are easier to use and absorb, comparable to regular pills. Recently, the FDA approved zolmitriptan, a medication with tolerability comparable to sumatriptan. Whereas zolmitriptan is only available as an oral melt or tablet, sumatriptan is available as a nasal spray, oral preparation, or self-injectable kit. The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine. However, zolmitriptan binds to plasma proteins only 25% of the time because of significant first-pass degradation. Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features.