Drug Targeting to the Lung: Chemical and Biochemical Considerations
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Structural modification of the antihistamine azatadine (10a) by replacing the N-methyl group with various carbamate groups eliminates CNS activity (Villani et al. 1986). Loratidine (10b), the most potent compound in this series of carbamates, shows no sedation liability in experimental animals and binds selectively to peripheral histamine receptors (Ahn and Barnett 1986). Other non-sedatory H1 antihistamines are temelastine (11), tazifylline (12), cetrizine (13), levocabastine (14), and epinastine (15) (Brown et al. 1986, Nicholson and Stone 1986, deVos et al. 1986). Tazifylline is reported to have ten times the bronchodilator activity exhibited by either astemizole or terfenadine. The pre-clinical pharmacology of AHR-11325 (16) and PR 1036-654 (17) suggests that both these new compounds are potent, non-sedating, long-acting H1 antagonists (Nolan et al. 1989, Palmer et al. 1989). Ebastine (18a), a structural analogue of terfenadine, has been reported to be a potent, selective, long-lasting antihistamine devoid of sedation at an oral dose of 10 mg (Vincent et al. 1988). Its mode of action is thought to be due to metabolism to the active form (18b) (Vincent et al. 1988).
Pharmacokinetic-Pharmacodynamic Correlations of Antihistamines
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Ebastine is a new histamine H1-antagonist which is extensively metabolized to its carboxylic acid metabolite carebastine, which appears to exert most, if not all, of the pharmacological actions. Vincent et al.71 investigated the pharmacokinetics, the antihistaminic effects, and the plasma concentration-effect relationship of ebastine in healthy subjects after a single oral dose of 10 and 50 mg. The pharmacokinetics of the metabolite carebastine was linear in the dose range studied and the terminal half-life averaged 10.6 and 12.5 h after 10 and 50 mg ebastine, respectively.
Carbopol emulgel loaded with ebastine for urticaria: development, characterization, in vitro and in vivo evaluation
Published in Drug Delivery, 2022
Barkat Ali Khan, Arshad Ali, Khaled M. Hosny, Abdulrahman A. Halwani, Alshaimaa M. Almehmady, Muhammad Iqbal, Waleed S. Alharbi, Walaa A. Abualsunun, Rana B. Bakhaidar, Samar S. A. Murshid, Muhammad Khalid Khan
The topical drug delivery system is considered to be an important therapeutic technique for skin disorders. It minimizes the chances of systemic toxicity and provides a quick onset of action compared with oral therapy. Ebastine is a second-generation H1 antagonist antihistamine drug that is prescribed for all types of allergies. It is especially the drug of choice for urticaria and allergic rhinitis. To overcome the side effects associated with oral ebastine therapy and to achieve benefits related to topical therapy, ebastine topical gels were prepared and evaluated successfully. From the results of the study, we concluded that an ebastine emulgel formulation prepared with Carbopol 940 showed acceptable physical characteristics upon storage for 28 days. The prepared emulgel showed excellent anti-allergic activity and high drug release when compared with the marketed cream. Therefore, ebastine emulgel can be used as topical anti-allergic therapy for the treatment of urticaria.
Down-titration of omalizumab in a patient with chronic spontaneous urticaria
Published in Journal of Dermatological Treatment, 2018
Pinuccia Omodeo
A 22-year-old man reported dermographism with frequent episodes of itching wheals, triggered by scratching or pressure, without angioedema, in 2011. He had allergic conjunctivitis and rhinitis and had received four runs of allergen-specific immunotherapy for Dermatophagoides, the year before. Symptoms improved after ebastine 10 mg administration. Some laboratory examinations were performed. Complete blood count was normal. Erythrocyte sedimentation rate, C reactive protein, urea, creatinine, transaminase, triglycerides, cholesterol, antistreptolysin title, and blood proteins electrophoresis were normal. C3 level was 0.96 g/L. C4 was 0.11 g/L (normal range = 0.2–0.5). Antinuclear antigen, anti-DNA antibodies, and anti-Helicobacter pylori antibodies were absent. Thyroid function tests were normal. Parasitologic examination of feces and anti HCV antibodies was negative. Specific IgE levels were Dermatophagoides = 50 kU/L, Phleum pratensis = 0.30 kUA/L, Parietaria officinalis = 0.13 kUA/L, and shrimp = 0.29 kUA/L.
Local immune response as novel disease mechanism underlying abdominal pain in patients with irritable bowel syndrome
Published in Acta Clinica Belgica, 2022
J. Aguilera-Lizarraga, M. Florens, H. Hussein, G. Boeckxstaens
The concept of food-mediated VHS proposed has major implications with respect to exploring novel treatments for IBS and related disorders. Our findings indicating H1R-mediated sensitization of visceral afferents [55] is in line with our previous pilot study evaluating the effect of the H1R receptor antagonist ebastine [54]. In this study, 55 IBS patients were enrolled in a placebo-controlled double-blind and randomized trial evaluating the effect of 12 weeks treatment with the H1R-antagonist ebastine. Of note, 46% of ebastine treated patients reported at least considerable relief (primary outcome) compared to 13% of placebo treated patients, yielding a therapeutic gain of 33%. A phase II study is ongoing to confirm this pilot study. Moreover, our findings set the stage for further studies exploring the potential of therapies targeting upstream mechanisms of mast cell-sensitization and/or activation, such as IgE neutralization or spleen tyrosine kinase (Syk) inhibitors, as the latter is a pivotal signaling transducer coupling antigen-IgE/FcεRI complexes regulating mast cell degranulation.
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