Comparison of Peripheral and Central Effects of Single and Repeated Oral Dose Administrations of Bilastine, a New H1 Antihistamine

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.

The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria

“…Colors of circles for desloratadine are as follows: 5 mg, pale green, 10 mg, mid green, and 20 mg, dark green (total, 38 patients). second-generation antihistamines after 4 to 5 days of administration has been reported repeatedly, [28][29][30] and the weekly stepwise increase in dosage in this study would be ideal to induce tolerance.…”

The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber

“…In clinical studies, bilastine has been shown to have a rapid onset of action and a long duration of effect [10,11]. Furthermore, bilastine has been shown to be free of cardiotoxicity [12] and sedative effects within the CNS and not to enhance the effects of lorazepam [13], the latter property supported by the observation that bilastine is a substrate for P-glycoprotein, an organic anion transporting protein (OATP) that prevents its uptake across the bloodbrain barrier into the brain [14].…”

Bilastine: A New Nonsedating Oral H1 Antihistamine for Treatment of Allergic Rhinoconjunctivitis and Urticaria

“…Non-sedating antihistamines do not generally have the effect, although this has been reported by few patients [23, 24]. A double-blinded, placebo-controlled study assessed the influence of bilastine 20, 40, and 80 mg and the sedating anti-histamine hydroxyzine hydrochloride 25 mg on psychomotor functions, when the drugs were taken by healthy subjects with standardized alcohol consumption [25]. Psychomotor functions were measured with objective tests and subjective assessment.…”