D2.239 - Oral and parenteral bilastine, fast onset and strong peripheral antihistaminic activity: comparison with oral second-generation antihistamines and intramuscular dexchlorpheniramine in wheal and flare models

Fast peripheral H1-receptor blockade is a key determinant of early symptom relief in allergic diseases. The histamine-induced wheal and flare (W&F) model is a validated pharmacodynamic (PD) tool to assess onset, magnitude and duration of action as well as itching perception reduction. Oral and parenteral bilastine formulations have been investigated using comparable W&F methodologies, allowing direct comparison with other first- and second-generation antihistamines (AHs). The aim of this study is to  evaluate and compare onset and magnitude of peripheral antihistaminic activity and itching reduction of oral and parenteral (intramuscular, i.m, and intravenous, i.v.) bilastine versus i.m. dexchlorpheniramine and oral AHs.

An integrated analysis was performed using data from randomized W&F (skin prick test or intradermal histamine) clinical studies. Histamine W&F were induced by prick test or intradermal injection. Treatments included oral bilastine 20 mg (fasting and fed), i.m. and i.v. bilastine, i.m. dexchlorpheniramine, oral AHs at standard doses and placebo. Outcomes included percentage inhibition of W&F areas and itching perception assessed by visual analogue scale (VAS) over time.

Across studies, oral bilastine  20 mg showed a consistently fast onset of action, with significant versus placebo W&F inhibition observed as early as 15 minutes post-dose in the most recent W&F trial, comparing oral and parenteral bilastine with parenteral dexchlorpheniramine. Oral bilastine also consistently achieved greater W&F inhibition and itch relief than i.m. dexchlorpheniramine despite its oral administration. Remarkably, dexchlorpheniramine did not exceed 25 % inhibition at any time, showing poorer and shorter effects compared to all bilastine formulations. Moreover, bilastine was not associated with sedation or psychomotor impairment, while dexchlorpheniramine showed high drowsiness scores and worse performance in psychomotor tests, potentially affecting tasks requiring sustained attention and rapid response.

Bilastine provides fast, strong, safe and sustained peripheral antihistaminic efficacy across oral and parenteral formulations. Oral bilastine demonstrates superior early peripheral efficacy compared with i.m. dexchlorpheniramine while maintaining a favourable central nervous system safety profile, supporting its use as an effective and as fast alternative to a widely used first-generation parenteral AH.