Background and objective: Ebastine is a long-acting, second-generation selective histamine H1 receptor antagonist. The pharmacodynamics of a new 10mg fast-dissolving tablet (FDT) oral lyophilisate tablet formulation of ebastine were compared with those of desloratadine and placebo following histamine skin intradermal test challenge. The acceptability of the FDT was also assessed.
Methods: This was a double-blind, double-dummy, placebo-controlled, randomised, crossover, three-period study in 36 healthy adults. The histamine skin intradermal test (0.05mL of 100 μg/mL solution) was administered into volunteers’ forearms, and wheal area was measured 15 minutes later. Ebastine 10mg FDT, desloratadine 5mg capsule or placebo were given on days 1–5. On day 1, a skin intradermal test was performed at baseline, then every 20 minutes for 2 hours after administration and at 24 hours. The final skin intradermal test was on day 6, 24 hours after the last drug dose. Subjective symptoms (itching, heat and pain) were assessed on day 1 for 2 hours following the first drug dose. There was a washout period of 7–10 days between treatments. At study end, the acceptability of the new ebastine formulation was evaluated using a questionnaire.
Results: Ebastine 10mg inhibited the wheal response to histamine significantly more than desloratadine 5mg or placebo 24 hours after 5 days’ treatment (mean difference between treatments in wheal area reduction from baseline: 26.7%, p < 0.0001; 46.9%, p < 0.0001, respectively), and after 24 hours on day 1 (mean difference: 16.2%, p = 0.0082; 34.2%, p < 0.0001, respectively). The results with desloratadine were also significantly different from placebo on day 1 and after 5 days, but less than with ebastine after 5 days (difference, desloratadine vs placebo: 20.2%, p = 0.0001). No differences in itching, heat and pain were observed between the treatments. Most participants (70%) preferred the FDT, and all reported that it made adherence easier.
Conclusion: Ebastine 10mg FDT demonstrated significantly superior antihistamine activity compared with desloratadine and placebo.
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This study received funding from Almirall SA. Mr Esbri and Dr Fortea are employees of Almirall SA, the company that manufactures ebastine. The other authors have no conflicts of interest that are directly relevant to the content of this study.
Storms WW. Clinical studies of the efficacy and tolerability of ebastine 10 or 20mg once daily in the treatment of seasonal allergic rhinitis in the US. Drugs 1996; 52Suppl. 1: 20–5PubMedCrossRefGoogle Scholar
Frank Jr H, Gillen M, Rohatagi SS, et al. A double blind, placebo controlled study of the efficacy and safety of ebastine 20mg once daily given with and without food in the treatment of seasonal allergic rhinitis. J Clin Pharmacol 2002; 42: 1097–104PubMedCrossRefGoogle Scholar
Hampel Jr F, Howland 3rd W, Van Bavel J, et al. A randomized, double blind, placebo controlled study comparing the efficacy and safety of ebastine (20mg and 10mg) to loratadine 10mg once daily in the treatment of seasonal allergic rhinitis. J Invest Allergy Clin Immunol 2004; 14: 56–63Google Scholar
Ratner P, Hampel Jr F, Gispert J. Efficacy of ebastine in the control of nasal congestion associated with allergic rhinitis. Methods Find Exp Clin Pharmacol 2003; 25: 111–5PubMedCrossRefGoogle Scholar
Ratner P, Hampel Jr F, Van Bavel J, et al. Efficacy and safety of ebastine 20mg compared to loratadine 10mg once daily in the treatment of seasonal allergic rhinitis: a randomized, double blind, placebo controlled study. Int Arch Allergy Immunol 2004; 133: 371–9PubMedCrossRefGoogle Scholar
Picado Valles C, Cadahia Garcia A, Cistero Bahima A, et al. Ebastine in perennial allergic rhinitis. Ann Allergy 1991; 67: 615–8PubMedGoogle Scholar
Bousquet J, Gaudano EM, Palma Carlos AG, et al. A 12 week, placebo controlled study of the efficacy and safety of ebastine, 10 and 20mg once daily, in the treatment of perennial allergic rhinitis. Multicentre Study Group. Allergy 1999; 54: 562–8PubMedCrossRefGoogle Scholar
Peyri J, Vidal J, Marrón J, et al. Ebastine in chronic urticaria: a double blind placebo controlled study. J Dermatol Treat 1991; 2: 51–3CrossRefGoogle Scholar
Kalis B. Double blind multicentre comparative safety study of ebastine, terfenadine and placebo in the treatment of chronic idiopathic urticaria. Drugs 1996; 52Suppl. 1: 30–4PubMedCrossRefGoogle Scholar
Gehanno P, Bremard-Oury C, Zeisser P. Comparison of ebastine to cetirizine in seasonal allergic rhinitis in adults. Ann Allergy Asthma Immunol 1996; 76: 507–12PubMedCrossRefGoogle Scholar
Ratner PH, Lim JC, Georges GC. Comparison of once daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and placebo in the treatment of seasonal allergic rhinitis. The Ebastine Study Group. J Allergy Clin Immunol 2000; 105: 1101–7PubMedCrossRefGoogle Scholar
Ratner P, Falques M, Chuecos F, et al. Meta analysis of the efficacy of ebastine 20mg compared to loratadine 10mg and placebo in the symptomatic treatment of seasonal allergic rhinitis. Int Arch Allergy Immunol 2005; 138: 312–8PubMedCrossRefGoogle Scholar
Vincent J, Limiñana R, Meredith PA, et al. The pharmacokinetics, antihistamine and concentration effect relationship of ebastine in healthy subjects. Br J Clin Pharmacol 1988; 26: 497–502PubMedCrossRefGoogle Scholar
Lasseter KC, Dilzer SC, Vargas R, et al. Pharmacokinetics and safety of ebastine in patients with impaired hepatic function compared with healthy volunteers: a phase I open label study. Clin Pharmacokinet 2004; 43: 121–9PubMedCrossRefGoogle Scholar
Van Cauwenberge P, De Beider T, Sys L. A review of the second generation antihistamine ebastine for the treatment of allergic disorders. Expert Opin Pharmacother 2004; 5: 1807–13PubMedCrossRefGoogle Scholar
Gillen MS, Miller B, Chaikin P, et al. Effects of supratherapeutic doses of ebastine and terfenadine on the QT interval. Br J Clin Pharmacol 2001; 52: 201–4PubMedCrossRefGoogle Scholar
Malik M. Effects of supratherapeutic doses of ebastine and terfenadine on the QT interval. Br J Clin Pharmacol 2002; 54: 682–3PubMedCrossRefGoogle Scholar
Fu Y, Yang S, Jeong SH, et al. Orally fast disintegrating tablets: developments, technologies, taste masking and clinical studies. Crit Rev Ther Drug Carrier Syst 2004; 21: 433–76PubMedCrossRefGoogle Scholar
Salvà M, Carreño B, Pintos M, et al. Phase I, single dose, open label, randomized, crossover bioequivalence studies of ebastine 10 and 20mg fast dissolving tablets in healthy male volunteers. Interasma-EAACI Joint Meeting Bilbao 28 November 2004. Poster OC9Google Scholar
Skassa Brociek W, Manderscheid JC, Michel FB, et al. Skin test reactivity to histamine from infancy to old age. J Allergy Clin Immunol 1987; 80: 711–6PubMedCrossRefGoogle Scholar
Van Niekerk CH, Prinsloo AEM. Effect of skin pigmentation on the response to intradermal histamine. Int Arch Allergy Appl Immunol 1985; 76: 73–5PubMedCrossRefGoogle Scholar
Antonijoan RM, Garcia Gea C, Puntes M, et al. Ebastine oral lyophilisate 20mg is superior to desloratadine 5mg or placebo in inhibiting the cutaneous reaction to histamine in healthy adults. Swiss Med Weekly 2006; 136(S149): 26S (P31)Google Scholar
Meltzer EO, Prenner BM, Nayak A. Efficacy and tolerability of once daily 5mg desloratadine, an H-receptor antagonist, in patients with seasonal allergic rhinitis: assessment during the spring and fall allergy seasons. Clin Drug Invest 2001; 21: 25–32CrossRefGoogle Scholar
Desager JP, Horsmans Y. Pharmacokinetic pharmacodynamic relationships of H1-antihistamines. Clin Pharmacokinet 1995; 28(5): 419–32PubMedCrossRefGoogle Scholar
Herron JM, Padhi D, Affrime MB, et al. Dose proportionality, linearity, and pharmacokinetics of desloratadine in healthy adults (abstract 1126). J Allergy Clin Immunol 2000; 104 (Suppl. 1 Pt 2): S385CrossRefGoogle Scholar
Demoly P, Michel FB, Bousquet J. In vivo methods for study of allergy, skin tests: techniques and interpretation. In: Middleton Jr E, Reed C, Ellis EF, et al., editors. Allergy: principles and practice. 5th ed. London: Mosby; 1998: 430–9Google Scholar
Grant JA, Danielson L, Rihoux JP, et al. A double blind, single dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine induced wheal and flare response for 24h in healthy male subjects. Allergy 1999; 54: 700–7PubMedCrossRefGoogle Scholar
Frossard N, Benabdesselam O, Purohit A, et al. Activity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady treatment in the skin of healthy volunteers. Fund Clin Pharmacol 2000; 14: 409–13CrossRefGoogle Scholar
Denham KJ, Boutsiouki P, Clough GF, et al. Comparison of the effects of desloratadine and levocetirizine on histamine induced wheal, flare and itch in human skin. Inflamm Res 2003; 52: 424–7PubMedCrossRefGoogle Scholar
Monroe EW, Daly AF, Shalhoub RF. Appraisal of the validity of histamine induced wheal and flare to predict the clinical efficacy of antihistamines. J Allergy Clin Immunol 1997; 99: S798–806PubMedCrossRefGoogle Scholar
Barbanoj MJ, Garcia Gea C, Morte A, et al. Central and peripheral evaluation of rupatadine, a new antihistamine/platelet activating factor antagonist, at different doses in healthy volunteers. Neuropsychobiology 2004; 50: 311–21PubMedCrossRefGoogle Scholar
Barbanoj MJ, Antonijoan RM, Garcia Gea C, et al. A study comparing the inhibitory effects of single and repeated oral doses of ebastine and fexofenadine against histamine induced skin reactivity. Int Arch Allergy Immunol 2003; 132: 263–7PubMedCrossRefGoogle Scholar
Gispert J, Antonijoan R, Barbanoj M, et al. Efficacy of ebastine, cetirizine, and loratadine in histamine cutaneous challenges. Ann Allergy Asthma Immunol 2002; 89: 259–64PubMedCrossRefGoogle Scholar