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      Assessment Of Spanlastic Vesicles Of Zolmitriptan For Treating Migraine In Rats

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          Abstract

          Objective

          To develop and evaluate zolmitriptan spanlastics (Zol SLs) as a brain-targeted antimigraine delivery system. Spanlastics (SLs) prepared using span 60: tween 80 (70:30%, respectively) gave the highest percentage of entrapment efficiency (EE%).

          Materials and methods

          A total of 60 adult male Wistar albino rats were divided into six groups (n=10 rats/group). Group 1 (Control) comprised rats serving as a negative control. Group 2 was treated with glyceryl trinitrate (NTG) and served as the positive control. Groups 3 (NTG+Zol com), Group 4 (NTG+Zol sol) and Group 5 (NTG+Zol SLs) received commercial zolmitriptan orally, zolmitriptan solution intranasally and Zol SLs F5 intranasally, respectively, 30 min before NTG. Group 6 (Zol SLs) comprised normal rats that received only Zol SLs intranasally.

          Results

          We found decreased T max, increased C max, AUC 0–6, AUC 0–∞ and ameliorated behaviour in rats (head scratching) treated with intranasal SLs compared to oral commercial zolmitriptan.

          Conclusion

          Our study substantiates the enhanced efficacy of Zol SLs in brain targeting for migraine treatment.

          Most cited references38

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          PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel.

          This study presents PKSolver, a freely available menu-driven add-in program for Microsoft Excel written in Visual Basic for Applications (VBA), for solving basic problems in pharmacokinetic (PK) and pharmacodynamic (PD) data analysis. The program provides a range of modules for PK and PD analysis including noncompartmental analysis (NCA), compartmental analysis (CA), and pharmacodynamic modeling. Two special built-in modules, multiple absorption sites (MAS) and enterohepatic circulation (EHC), were developed for fitting the double-peak concentration-time profile based on the classical one-compartment model. In addition, twenty frequently used pharmacokinetic functions were encoded as a macro and can be directly accessed in an Excel spreadsheet. To evaluate the program, a detailed comparison of modeling PK data using PKSolver and professional PK/PD software package WinNonlin and Scientist was performed. The results showed that the parameters estimated with PKSolver were satisfactory. In conclusion, the PKSolver simplified the PK and PD data analysis process and its output could be generated in Microsoft Word in the form of an integrated report. The program provides pharmacokinetic researchers with a fast and easy-to-use tool for routine and basic PK and PD data analysis with a more user-friendly interface. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
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            The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies.

            The study aims to provide an updated assessment of the evidence for individual pharmacological therapies for acute migraine treatment. Pharmacological therapy is frequently required for acutely treating migraine attacks. The American Academy of Neurology Guidelines published in 2000 summarized the available evidence relating to the efficacy of acute migraine medications. This review, conducted by the members of the Guidelines Section of the American Headache Society, is an updated assessment of evidence for the migraine acute medications. A standardized literature search was performed to identify articles related to acute migraine treatment that were published between 1998 and 2013. The American Academy of Neurology Guidelines Development procedures were followed. Two authors reviewed each abstract resulting from the search and determined whether the full manuscript qualified for review. Two reviewers studied each qualifying full manuscript for its level of evidence. Level A evidence requires at least 2 Class I studies, and Level B evidence requires 1 Class I or 2 Class II studies. The specific medications - triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan [oral, nasal spray, injectable, transcutaneous patch], zolmitriptan [oral and nasal spray]) and dihydroergotamine (nasal spray, inhaler) are effective (Level A). Ergotamine and other forms of dihydroergotamine are probably effective (Level B). Effective nonspecific medications include acetaminophen, nonsteroidal anti-inflammatory drugs (aspirin, diclofenac, ibuprofen, and naproxen), opioids (butorphanol nasal spray), sumatriptan/naproxen, and the combination of acetaminophen/aspirin/caffeine (Level A). Ketoprofen, intravenous and intramuscular ketorolac, flurbiprofen, intravenous magnesium (in migraine with aura), and the combination of isometheptene compounds, codeine/acetaminophen and tramadol/acetaminophen are probably effective (Level B). The antiemetics prochlorperazine, droperidol, chlorpromazine, and metoclopramide are probably effective (Level B). There is inadequate evidence for butalbital and butalbital combinations, phenazone, intravenous tramadol, methadone, butorphanol or meperidine injections, intranasal lidocaine, and corticosteroids, including dexamethasone (Level C). Octreotide is probably not effective (Level B). There is inadequate evidence to refute the efficacy of ketorolac nasal spray, intravenous acetaminophen, chlorpromazine injection, and intravenous granisetron (Level C). There are many acute migraine treatments for which evidence supports efficacy. Clinicians must consider medication efficacy, potential side effects, and potential medication-related adverse events when prescribing acute medications for migraine. Although opioids, such as butorphanol, codeine/acetaminophen, and tramadol/acetaminophen, are probably effective, they are not recommended for regular use.
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              Characterization of a novel model of chronic migraine.

              Chronic migraine is a disabling condition that affects hundreds of millions of individuals worldwide. The development of novel migraine treatments has been slow, in part as a result of a lack of predicative animal models. We have developed a new model of chronic migraine involving the use of nitroglycerin (NTG), a known migraine trigger in humans. Chronic intermittent administration of NTG to mice resulted in acute mechanical hyperalgesia with each exposure as well as a progressive and sustained basal hyperalgesia. This chronic basal hyperalgesia occurred in a dose-dependent fashion and persisted for days after cessation of NTG administration. NTG-evoked hyperalgesia was exacerbated by the phosphodiesterase 5 inhibitor sildenafil, also a human migraine trigger, consistent with nitric oxide as a primary mediator of this hyperalgesia. The acute but not the chronic basal hyperalgesia was significantly reduced by the acute migraine therapy sumatriptan, whereas both the acute and chronic hyperalgesia was significantly attenuated by the migraine preventive therapy topiramate. Chronic NTG-induced hyperalgesia is a mouse model that may be useful for the study of mechanisms underlying progression of migraine from an episodic to a chronic disorder, and for the identification and characterization of novel acute and preventive migraine therapies.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                21 November 2019
                2019
                : 13
                : 3929-3937
                Affiliations
                [1 ]National Egyptian Center of Environmental & Toxicological Research (NECTR), Faculty of Medicine, Cairo University , Cairo, Egypt
                [2 ]Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University , Cairo, Egypt
                [3 ]Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Fayoum University , Elfayoum, Egypt
                Author notes
                Correspondence: Nagla Ahmed El-Nabarawy National Egyptian Center of Environmental & Toxicological Research (NECTR), Faculty of Medicine, Cairo University , Kasr A Ainy Street, Cairo11562, Egypt Email n.a.nabarawy@gmail.com
                Author information
                http://orcid.org/0000-0003-4657-5777
                http://orcid.org/0000-0002-7565-301X
                Article
                220473
                10.2147/DDDT.S220473
                6877729
                31819367
                27677c96-4cad-48cc-bc3e-a4d4e2af9c77
                © 2019 El-Nabarawy et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 22 June 2019
                : 21 October 2019
                Page count
                Figures: 4, Tables: 3, References: 48, Pages: 9
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                zolmitriptan,zol,intranasal delivery,brain targeting,spanlastics,sls,pharmacokinetics,pharmacodynamics,migraine

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