Eletriptan Research Articles

Nose-to-brain delivery of nano-engineered biomaterials for effective targeting to the brain

Thermoresponsive hydrogels provide a platform for sustained delivery of nanoparticles via nose-to-brain route by resisting mucociliary clearance to the enhanced mean residence time (MRT) of the formulation in the nasal cavity overcoming neurotoxicity induced by uncontrolled delivery of nanoparticles and accumulation in the brain when delivered alone. The reported study presents the synthesis of pullulan (PLN) based nanoparticles (PNP-EHBr) loaded with eletriptan hydrobromide (EHBr) via ionic gelation method having size between 26.65 nm and 29.59 nm after stability studies of 4 h incubation with an average zeta potential of 22.5 ± 0.1 mV and entrapment efficiency of 92.048%. F-127/F-68 based hyaluronic acid-co-pectin hydrogels of EHBr-loaded PLN nanoparticles thermoresponsive hydrogels (HAP-PNP-EHBr/T-Hg) were characterized via Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis (TGA/DSC), and scanning electron microscopy and evaluated for their gelation time, gelation temperature, gel strength, cloud point, sol–gel fraction, ex-vivo permeation, etc. HAP-PNP-EHBr/T-Hg showed drug release in a controlled pattern in both phosphate-buffered saline (PBS) and simulated nasal fluid (SNF) i.e., 90.12 and 87.99, respectively, over 48 h, while PNP-EHBR, 99.44 and 97.53 in PBS and SNF, respectively, over 8 h. The controlled release and absorption of EHBr from HAP-PNP-EHBr/T-Hg and PNP-EHBr was estimated by an in-vivo pharmacokinetic study using high-performance liquid chromatography, MRT and area under the curve (AUC) were increased up to 11.337 ± 0.32 h and 3,104.73 ± 75.841 ng/mL*h, 11.088 ± 0.177 h and 3,906.64 ± 152.86 ng/mL*h in brain and blood respectively after IN administration. This work demonstrates the successful synthesis of a twofold drug delivery system with PLN-based nanoparticles (PNP-EHBr) loaded with EHBr laden F-127/F-68 based hyaluronic acid-co-pectin hydrogels (HAP-PNP-EHBr/T-Hg).

Formulation and Evaluation of Nasal in situ Gel of Eletriptan Hydrobromide

Formulation and Evaluation of Nasal in situ Gel of Eletriptan Hydrobromide

Facile and green chemistry-compatible fluorescence spectroscopic applications of acid red 87 used to evaluate eletriptan, antimigraine, in its pharmaceutical and biological samples

Eletriptan (ETR), a selective pharmaceutical agent agonist of the 5-hydroxytryptamine1 receptor subtype, are primarily used to treat acute migraine attacks. ETR is a triptan-class medication that works by narrowing cerebral blood vessels and reducing chemicals that produce headache pain, light and sound sensitivity, and nausea. Due to its effectiveness in reducing migraine symptoms, it is a worthwhile choice for those looking for quick and efficient treatment. A green, raid, one-pot and straightforward fluorescence spectrometric method was employed to evaluate ETR in tablets and biological samples. By introducing the ETR drug and the fluorescent ligand, Acid red 87, in an acidic buffer, a quenching of the ligand native fluorescent was promptly produced. The quenching action was simply attributed to the selective ion-pair complex generation between the cationic target and the selected ligand. An increase in ETR concentration was linearly proportional to the quenching response in the 50.0 – 500.0 ng/mL range. The optimal configurations for adjusting the system's variable parameters were determined by examining the ETR–Acid red 87 system's response. Additionally, the sensor that was developed met the standards set by the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. The sensitivity thresholds of the approach were 13.8 and 42.0 ng/mL for the detection and quantification parameters, respectively, LOD and LOQ. This approach proficiently evaluated the pharmaceutical and biological samples of ETR. Finally, the proposed approach not only simplifies the analysis process but also limits the badimpact on the environment, making it a promising technique for analytical applications.

Design Optimization and Pharmacokinetic Study of Eletriptan Hydrobromide Loaded Solid Lipid Nanoparticle Nasal Gel Targeted to Brain

In the present research work, Eletriptan Hydrobromide(E-HBr)-loaded solid lipid nanoparticles (SLN’s) incorporated in a gel was prepared by emulsification solvent evaporation technique to enhance the uptake of E-HBr to brain via intra-nasal (i.n.) route and the formulations were evaluated for particle size, polydispersibility index, zeta potential, drug entrapment efficiency, in-vitro drug release, and stability of the optimized formulation. All the parameters evaluated were within the acceptable range. In-vitro drug release for the optimized gel formulation was found to be 92.45% after 12hr and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.995). Pharmacokinetics studies were performed on albino male Wistar rats and the concentration of E-HBr in brain and blood plasma was measured by HPLC. The brain/blood ratio at 0.5h for E-HBr Opt.SLN’s i.n., E-HBr sol. i.n., and E-HBr sol. oral. were found to be 2.35, 1.19 and 0.80 respectively, indicating the drug transported directly from nose-to-brain, by bypassing the blood–brain barrier in the olfactory region present in the nasal cavity. The maximum concentration of drug in brain (Cmax) after i.n. administration of E-HBr-SLN gel was found to be (21465.87±1110.66ng/ml, Tmax 8.45hr) significantly higher than that achieved after oral administration (6797.23±842.86ng/ml, Tmax 7hr), and i.n. (16451.53±3792.40ng/ml, Tmax 7.69 hr) administration of E-HBr sol. The highest drug-targeting efficiency (2.35%) and direct transport percentage (66.05%) was found with E-HBr-SLN’s as compared to the other formulations. Higher DTE (%) and DTP (%) suggest, that E-HBr-SLN gel had better brain targeting efficiency as compared to other formulations.

Statistically Optimized Polymeric Buccal Films of Eletriptan Hydrobromide and Itopride Hydrochloride: An In Vivo Pharmacokinetic Study.

A migraine is a condition of severe headaches, causing a disturbance in the daily life of the patient. The current studies were designed to develop immediate-release polymeric buccal films of Eletriptan Hydrobromide (EHBR) and Itopride Hydrochloride (ITHC) to improve their bioavailability and, hence, improve compliance with the patients of migraines and its associated symptoms. The prepared films were evaluated for various in vitro parameters, including surface morphology, mechanical strength, disintegration test (DT), total dissolving time (TDT), drug release and drug permeation, etc., and in vivo pharmacokinetic parameters, such as area under curve (AUC), mean residence time (MRT), half-life (t1/2), time to reach maximum concentration (Tmax), and time to reach maximum concentration (Cmax). The outcomes have indicated the successful preparation of the films, as SEM has confirmed the smooth surface and uniform distribution of drugs throughout the polymer matrix. The films were found to be mechanically stable as indicated by folding endurance studies. Furthermore, the optimized formulations showed a DT of 13 ± 1 s and TDT of 42.6 ± 0.75 s, indicating prompt disintegration as well as the dissolution of the films. Albino rabbits were used for in vivo pharmacokinetics, and the outcomes were evident of improved pharmacokinetics. The drug was found to rapidly permeate across the buccal mucosa, leading to increased bioavailability of the drug: Cmax of 130 and 119 ng/mL of ITHC and EHBR, respectively, as compared to 96 (ITHC) and 90 ng/mL (EHBR) of oral solution. The conclusion can be drawn that possible reasons for the enhanced bioavailability could be the increased surface area in the form of buccal films, its rapid disintegration, and faster dissolution, which led toward the rapid absorption of the drug into the blood stream.

DESIGN, CHARACTERIZATION AND EVALUATION OF NOVEL MUCOADHESIVE NASAL INSERTS FOR THE TREATMENT OF MIGRAINE

Recently, nasal administration has gained more attention as a safe way for delivering the active ingredients used to treat migraines. Strategies can be implemented by changing aspects like the medicines, delivery vehicle, and other components to get around the obstacles associated with conventional therapies. This research work aimed to explore the potential of lyophilized nasal inserts of eletriptan hydrobromide for the treatment of migraine attack. Here, the lyophilization technique is used for the nasal inserts preparation. The developed inserts were tested for various characterization studies,such as mucoadhesive examinations, water uptake, in vitro drug release, in vitro cytotoxicity, ex vivo investigations and stability. The inserts showed acceptable pH values, satisfactory mucoadhesion potential and excellent water uptake activity. In vitro release data for the formulations followed first-order kinetics. The cytotoxicity studies showed that there was a reduction in cell toxicity of drug embedded in the inserts when compared to the pure drug. When the prepared nasal inserts were used for treatment, there was no significant impact on the epithelium of nasal mucosa. The novel lyophilized nasal inserts of eletriptan hydrobromide could be a better alternative for the treatment of migraine

Method development and validation for simultaneous determination of Eletriptan hydrobromide and Itopride hydrochloride from fast dissolving buccal films by using RP-HPLC

AbstractOne of the most effective, rapid, and simple methods reversed-phase high-performance liquid chromatography (RP-HPLC) was used for simultaneous development and validation of Eletriptan hydrobromide (ELE HBR) and Itopride hydrochloride (ITP HCL) in combination. The method was validated based on the regulations of United States Pharmacopeia (USP) and International Conference on Harmonization (ICH) guidelines. Separation of both drugs was achieved within approximately 5 min by using a mobile phase made up of a 70:30 ratio of phosphate buffer and acetonitrile having a flow rate of 1 mL min−1. Furthermore, a comprehensive study was conducted on precision, accuracy, linearity, inter-day, intra-day studies, an assay of formulated films, and stability studies of combined prepared film. Co-efficient of correlation ranged between 0.9993, and 0.9965 for ELE HBR and ITP HCL respectively. The accuracy of the developed method was accurate as drug recoveries in both cases of ITP HCL, and ELE HBR falls between (99.87, 99.96, and 99.84%) to (99.81, 99.12, and 98.44%) respectively having a concentration range of solutions between 10, 30 and 50 μg mL−1 dilution. Films developed by using both drugs in combination were then validated for assay studies, and it was found that substantial results of 99.05%, and 99.87% were found in the case of ITP HCL and ELE HBR respectively. The stability of the solution and mobile phase showed the method's accuracy as the results were 97% for ITP HCL and 99% for ELE HBR. The proposed method developed for simultaneous determination of ITP HCL and ELE HBR was developed and validation and no interaction of any excipient were found.

Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies.

Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4-5 cell layers with basal cells still undergoing mitosis. The optimum period at the air-liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes' differentiation and inflammatory conditions, etc.).

Oral transmucosal delivery of eletriptan for neurological diseases

Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

The Development of Eletriptan Hydrobromide Immediate Release Buccal Films Using Central Composite Rotatable Design: An In Vivo and In Vitro Approach.

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 ± 1.13), while a maximum of 92.87 ± 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 µm. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t½) of 4.54 ± 0.18 h and a Cmax of 128 ± 0.87 (ng/mL); Tmax was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively.

Formulation and Evaluation of Oral Trans-mucosal Delivery System of Eletriptan Hydrobromide

Formulation and Evaluation of Oral Trans-mucosal Delivery System of Eletriptan Hydrobromide

Chitosan/guar gum-based thermoreversible hydrogels loaded with pullulan nanoparticles for enhanced nose-to-brain drug delivery

The biopolymers-based two-fold system could provide a sustained release platform for drug delivery to the brain resisting the mucociliary clearance, enzymatic degradation, bypassing the first-pass hepatic metabolism, and BBB thus providing superior bioavailability through intranasal administration. In this study, poloxamers PF-127/PF-68 grafted chitosan HCl-co-guar gum-based thermoresponsive hydrogel loaded with eletriptan hydrobromide laden pullulan nanoparticles was synthesized and subjected to dynamic light scattering, Fourier transform infrared spectroscopy, thermal analysis, x-ray diffraction, scanning electron microscopy, stability studies, mucoadhesive strength and time, gel strength, cloud point assessment, rheological assessment, ex-vivo permeation, cell viability assay, histology studies, and in-vivo Pharmacokinetics studies, etc. It is quite evident that CSG-EH-NPs T-Hgel has an enhanced sustained release drug profile where approximately 86 % and 84 % of drug released in phosphate buffer saline and simulated nasal fluid respectively throughout 48 h compared to EH-NPs where 99.44 % and 97.53 % of the drug was released in PBS and SNF for 8 h. In-vivo PKa parameters i.e., mean residence time (MRT) of 11.9 ± 0.83 compared to EH-NPs MRT of 10.2 ± 0.92 and area under the curve (AUCtot) of 42,540.5 ± 5314.14 comparing to AUCtot of EH-NPs 38,026 ± 6343.1 also establish the superiority of CSG-EH-NPs T-Hgel.

Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms.

Migraine is one of the major symptoms of many psychiatric and mental disorders like depression and anxiety. Eletriptan Hydrobromide (EH) is a well-tolerated drug in migraine treatment, but suffers from low oral bioavailability and low brain targeting after oral delivery. New nasal mucoadhesive EH-emulsomes development could be a new means to direct the drug from the nose-to-brain to achieve rapid onset of action and high drug concentration in the brain for acute migraine treatment. Eletriptan mucoadhesive emulsomes formulations were prepared using thin-film hydration method and 23 full factorial design was adopted to study different formulation factors’ effect on the emulsomes characters. The emulsomes were characterized for entrapment efficiency (EE%), zeta potential (ZP), particle size (PS), morphology, and ex-vivo permeation through the nasal mucosa. The selected formula was evaluated in mice for its in-vivo bio-distribution in comparison with EH intranasal and intravenous solutions. Drug targeting efficacy (DTE%) and nose-to-brain direct transport percentage (DTP%) were calculated. The optimization formulation showed a nanoparticle size of 177.01 nm, EE 79.44%, and ZP = 32.12 ± 3.28 mV. In addition, in-vitro permeability studies revealed enhanced drug permeability with suitable mean residence time up to 120 ± 13 min. EH-emulsomes were stable under different storage conditions for three months. In vivo examination and pharmacokinetic drug targeting parameters revealed EH transport to the CNS after EH nanoparticle nasal administration. Histopathology study showed no ciliotoxic effect on the nasal mucosa. From the results, it can be confirmed that the emulsomes formulation of EH proved safe direct nose-to-brain transport of EH after nasal administration of EH emulsomes.

Bromine K-Edge X-Ray Absorption Near-Edge Structure Analysis on Hydrobromide-Salt Crystals and the Solid Dispersion of Active Pharmaceutical Ingredients.

Bromine K-edge X-ray absorption near-edge structure (XANES) spectroscopy analyses were used to evaluate the crystals of the active pharmaceutical ingredients, eletriptan hydrobromide, dextromethorphan hydrobromide and scopolamine hydrobromide salts and the solid dispersion of eletriptan hydrobromide. The crystals and the solid dispersion of the active pharmaceutical ingredient (API) salts could be discriminated based on the shape of the XANES spectra. The differences in the shape of XANES spectra was ascribable to the differences in the interatomic interactions of the bromine ions based on the crystal structures. Ratio of the eletriptan hydrobromide α-form crystal in mixed powders of α-form and monohydrate crystals could be quantified by the linear-combination fitting using their XANES spectra. These results indicated that the XANES spectroscopy are a potent method for evaluating the APIs of pharmaceutical formulations even at the higher energy region around the bromine K-edge of 13470 eV.

A novel LC-MS method development and validation for the determination of phenyl vinyl sulfone in eletriptan hydrobromide

BackgroundThe aim of the present method is to develop and validate a specific, sensitive, precise, and accurate liquid chromatography-mass spectrometry (LC-MS) method for the estimation of the phenyl vinyl sulfone in the eletriptan hydrobromide. The effective separation of the phenyl vinyl sulfone was achieved by the Symmetry C18 (50 × 4.6 mm, 3.5 μm) column and a mobile phase composition of 0.1%v/v ammonia buffer to methanol (5:95 v/v), using 0.45 ml/min flow rate and 20 μl of injection volume, with methanol used as diluent. The phenyl vinyl sulfone was monitored on atomic pressure chemical ionization mode mass spectrometer with positive polarity mode.ResultsThe retention time of phenyl vinyl sulfone was found at 2.13 min. The limit of detection (LOD) and limit of quantification (LOQ) were observed at 1.43 ppm and 4.77 ppm concentration respectively; the linear range was found in the concentration ranges from 4.77 to 27.00 ppm with regression coefficient of 0.9990 and accuracy in the range of 97.50–102.10%. The percentage relative standard deviation (% RSD) for six replicates said to be injections were less than 10%.ConclusionThe proposed method was validated successfully as per ICH guidelines. Hence, this is employed for the determination of phenyl vinyl sulfone in the eletriptan hydrobromide.

Development and validation of spectrophotometric methods for estimation of antimigraine drug eletriptan hydrobromide in pure form and pharmaceutical formulations

The present study aims to develop and validate four simple, sensitive, reproducible, and low-cost spectrophotometric methods for the determination of antimigraine drug (eletriptan hydrobromide) in pure form and pharmaceutical formulations. The methods are based on the formation of yellow colored ion-pair complex between eletriptan hydrobromide and four acid dyes, namely, bromocresol purple (BCP), bromocresol green (BCG), bromophenol blue (BPB), and bromothymol blue (BTB) with absorption maxima at 410, 420, 414 and 416nm, respectively. Several parameters such as pH, buffer type and volume, reagent volume, sequence of addition and effect of extracting solvent were optimized. Under the optimum experimental conditions, beer's law is obeyed over the concentration ranges of 1.0-20 and 1.0-16μgmL-1 for (BCP or BCG) and (BPB or BTB), respectively with good correlation coefficients (0.9995-0.9999). The apparent molar absorptivity and Sandell's sensitivity values are reported for all methods. The limit of detection (LOD) and the limit of quantification (LOQ) values are found to be 0.27, 0.28, 0.25, and 0.30μgmL-1 and 0.90, 0.93, 0.83, and 1.0μgmL-1 for BCP, BCG, BPB and BTB, respectively. The stoichiometric ratio of the formed ion-pair complexes was found to be 1:1 (drug: reagent) for all methods. The developed methods were successfully applied for the determination of eletriptan hydrobromide in pharmaceutical formulations with good accuracy and precision. Statistical comparison of the results was performed using Student's t-test and variance ratio F-test at the 95% confidence level and there was no significant difference between the reported and proposed methods regarding accuracy and precision. Further, the validity of the proposed methods was confirmed by recovery studies via standard addition method.

Eletriptan hydrobromide Orodispersible tablets: Design, Development and In vitro characterization

Eletriptan hydrobromide Orodispersible tablets: Design, Development and In vitro characterization

Nose to brain delivery of eletriptan hydrobromide nanoparticles: Preparation, in vitro/in vivo evaluation and effect on trigeminal activation

Migraine is a chronic disorder of the brain and acts through peripheral trigeminal activation. Thus, both central and peripheral stimulations can play a part in sensitization and activation of trigeminal neurons. Intranasal drug delivery offers a possible solution due to direct link to trigeminal nerves. A wide variety of therapeutic compounds can be administered intranasally for their topical, systemic and central nervous system (CNS) action. In this study, eletriptan hydrobromide (EH) loaded PLGA nanoparticles were prepared and their antimigraine activity was evaluated after intranasal administration. It was shown that PLGA nanoparticles had an average particle size of 201.5 ± 13.6 nm and zeta potential value of – 17.3 ± 2.11 mV. After cellular uptake and P-glycoprotein efflux studies, EH nanoparticles were shown to overcome P- glycoprotein mediated drug efflux. The pharmacokinetic parameters revealed a marked improvement in the CNS permeation behavior of intranasal EH loaded nanoparticle administration as compared to intravenous administration of drug (p < 0.05). There was two times higher AUCbrain representing a higher total amount of drug reaching to the brain (AUC0-∞ = 100.34 ± 29.13 ng/ml.h for intranasal nanoparticle administration and AUC0-∞ = 60.01 ± 11.30 ng/ml.h for intravenous solution). We showed that expressions of c-fos and substance P are dependent on the drug that reached to the brain and intranasal drug administration prolonged the expression of substance P and c-fos mRNA levels. Based on the results, intranasal PLGA nanoparticle administration of EH may be evaluated as a better treatment option for migraine therapy.

SAT-192 Eletriptan (RelpaxaTm) Causing False Positive Elevations in Urinary Metanephrine

Background:The diagnosis of pheochromocytoma depends crucially on the demonstration of excessive production of catecholamines. This step, however, is fraught with several difficulties, in particular with false-positive test results. Drugs such as phenoxybenzamine and tricyclic antidepressants are the most frequently associated causes for false-positive results. Other medications are also known to cause a false positive elevation of urinary metanephrines. We are reporting a patient with markedly elevated urine metanephrines associated with the use of Eletriptan hydrobromide (RelpaxaTM), a drug commonly used for treating migraine.Clinical Case:A 29-year-old man with a history of migraine managed on ibuprofen and recently started Eletriptan presented to the emergency room complaining of a 24-hour history of progressively worsening headaches. At the time of initial evaluation his blood pressure was in the 220s/160s with a creatinine of 1.9 mg/dL with unknown baseline. He was managed on an IV nicardipine drip. Due to his young age he underwent an evaluation for secondary causes of his hypertension. Laboratory: normal aldosterone/renin level (ratio was 0.4), normal midnight salivary cortisol and normal thyroid function studies. Urine screening for drug abuse was also negative. A 24-hour urine metanephrine level, while the patient was taking Eletriptan, was markedly elevated (normetanephrine 1341mcg (ref 82–500) and metanephrine level of 2494 mcg (ref 45–290). In contrast, the plasma metanephrines were only mildly elevated (metanephrines level 27 pg/ml (ref 0–62) and normetanephrine level of 255 pg/ml (ref 0–145)). Adrenal CT did not reveal any evidence of adrenal nodules. Additionally a Gallium-68 PET/CT scan did not reveal any evidence of pheochromocytoma or paraganglioma. Eletriptan was discontinued and his blood pressure was controlled on oral medications. Within one week of stopping Eletriptan his urine metanephrines (metanephrine 76 mcg/ 24 hrs, normetanephrine 277 mcg/dL) and plasma metanephrines (metanephrine 39 pg/mL, normetanephrine 148 pg/mL) normalized. Conclusion: The discrepancy between plasma and urine metanephrines in our patient suggests the possibility of a false positive test. Eletriptan, a second generation triptan drug, is a selective 5-hydroxytryptamine 1B/1D receptor agonist and has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. However, Eletriptan has no significant affinity or pharmacological activity at adrenergic α1, α2, or β; dopaminergic D1 or D2; muscarinic; or opioid receptors. It is also interesting to note that Eletriptan use is contraindicated in uncontrolled hypertension. It is possible Eletriptan may affect the assay of urine metanephrines. However, the exact mechanism of Eletriptan causing elevated urine metanephrines in our patient is not clear.

Development of Sustained Release Floating Tablet of Eletriptan Hydrobromide for Management of Migraine

Development of Sustained Release Floating Tablet of Eletriptan Hydrobromide for Management of Migraine