Comparison of Peripheral and Central Effects of Single and Repeated Oral Dose Administrations of Bilastine, a New H-1 Antihistamine A Dose-Range Study in Healthy Volunteers With Hydroxyzine and Placebo as Control Treatments
ABSTRACT Peripheral anti-H1 and central nervous system (CNS) activities after single (day 1) and repeated (day 7) administrations of increasing doses of bilastine (BIL) were assessed in 20 healthy volunteers throughout a crossover, randomized, double-blind, placebo (PLA)-controlled study. Repeated doses of BIL 20, 40, or 80 mg and hydroxyzine 25 mg (HYD) as positive standard were administered on 7 consecutive days. Before and at several time points after drug intake, skin reactivity to the intradermal injection of histamine, objective tests of psychomotor performance, and subjective mood scales were evaluated. All active treatments led to a significant and similar reduction in the wheal reaction in relation to PLA after both the single (P < 0.001) and repeated administrations (P < 0.001). No delay was observed in the onset of its peripheral activity after the first dose of BIL as compared with HYD. No tolerance or sensitization was seen when comparing acute and repetitive assessments. Central nervous system effects showed that HYD induced the greatest psychomotor impairment (P < 0.05). Repeated HYD intake showed a lower number of significant alterations in comparison to acute administration. Bilastine 80 mg also showed some impairment (P < 0.05). Subjectively, the only active treatment that could not be differentiated from PLA was BIL 20 mg. Hydroxyzine 25 mg showed the greatest differentiation (P < 0.01). A clear dissociation between peripheral anti-H1 and CNS activity was found after BIL treatment. Significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL. The 40-mg dose of BIL produced subjective report of sedation, whereas unwanted objective CNS side effects were observed only with the 80-mg dose.
SourceAvailable from: Cristoforo Incorvaia[Show abstract] [Hide abstract]
ABSTRACT: Bilastine is a new second generation H1-antihistamine recently approved for the symptomatic treatment of allergic rhinitis (AR) and chronic urticaria (CU). Bilastine epitomizes the evolution of research on antihistamines concerning both efficacy and safety. In AR treatment, a number of large controlled clinical trials documented its efficacy, as assessed by improvement of all nasal and ocular symptoms and quality of life. These outcomes show that bilastine meets current EAACI/ARIA criteria for medications used in the treatment of AR. Also in CU, the review of the literature indicates that once-daily treatment with bilastine 20 mg was effective in managing symptoms and improving patient's quality of life. Concerning safety and tolerability, the profile of bilastine is very similar to placebo and in particular the adverse effects on central nervous system are insignificant. The balance of efficacy and safety of bilastine is particularly helpful when dosages higher than standard are needed to control the symptoms, as frequently occurs in patients with urticaria, in whom antihistamines doses up to four times the standard dose may be administered.Clinical and Molecular Allergy 04/2015; 13(1):1. DOI:10.1186/s12948-015-0008-x · 1.39 Impact Factor
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ABSTRACT: Background: Allergic rhinitis is a very frequent disease. H1 antihistamines have been used for treatment of allergic rhinitis for more than 5 decades. They differ in chemical structure, pharmacokinetics, pharmacodynamics, clinical efficacy and adverse effects. Methods: We performed a detailed analysis of all available publications concerning the new H1-antihistamine bilasitine. Results: Bilastine, a piperidine derivative, is a novel potent H1 antihistamine. It is at least as potent as cetirizine or fexofenadine in in vitro studies. In animal studies it demonstrates dose-dependent antihistaminic and antiallergic effects. In humans its metabolism is not affected by age, gender or renal function but may be affected by coadministration of P glycoprotein inhibitors. Efficacy of bilastine in therapy of allergic rhinitis patients has been documented in several large controlled clinical trials showing bilastine being at least as effective as cetirizine or desloratadine. No significant suppressive effect on central nervous system could be demonstrated when bilastine was used in the recommended doses. Conclusion: Bilastine is a novel H1 antihistamine with anti-allergic properties which is highly effective in the treatment of symptoms of allergic rhinitis. It has a favorable pharmacokinetic and pharmacodynamic profile and is generally well tolerated.American journal of rhinology & allergy 08/2014; 28(4). DOI:10.2500/ajra.2014.28.4049 · 2.18 Impact Factor
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ABSTRACT: AimA close correlation exists between positron emission tomography (PET)-determined histamine H1-receptor occupancy (H1RO) and the incidence of sedation. Antihistamines with H1RO <20% are classified as nonsedating. The objective was to measure H1RO of bilastine, a new second-generation antihistamine, compared with that of hydroxyzine.Methods This randomized, double-blind, crossover study used PET imaging with [11C]doxepin to evaluate 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials (BP) and H1ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated.ResultsThe mean BP of all five regions of interest [TOTAL BP] was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, p< 0.01, mean difference and 95% CI: -0.130 [-0.155,-0.105]), with no significant difference between bilastine and placebo. Overall H1RO by bilastine was significantly lower than that by hydroxyzine (mean value –3.92% vs. 53.95%, p< 0.01, mean difference and 95% CI: 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and TOTAL BP values. No significant between-treatment group differences were observed regarding sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine or hydroxyzine.ConclusionsA single oral dose of bilastine 20 mg had minimal H1RO, was not linked with subjective sedation or objective impairment of psychomotor performance, and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective, and PET criteria as a nonsedating antihistamine.British Journal of Clinical Pharmacology 05/2014; 78(5). DOI:10.1111/bcp.12421 · 3.69 Impact Factor