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Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults and children aged ≥ 6 years. Pharmacokinetic data for children aged 6-11 years were extracted post hoc from a study in which children (2-11 years) with allergic rhinoconjunctivitis or urticaria received oral bilastine (10 mg/day). Maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC) data were compared with adult pharmacokinetic data from seven clinical studies (bilastine 20 mg/day). Safety data for children aged 6-11 years were extracted post hoc from a phase III randomized controlled trial of children (2-11 years) with allergic rhinoconjunctivitis or chronic urticaria receiving once-daily bilastine 10 mg or placebo for 12 weeks. Exposure and Cmax values were similar for children (6-11 years) and adults: median pediatric/adult ratios for AUC0-24 and Cmax were 0.93 and 0.91, respectively. There was no significant difference in the incidence of treatment-emergent adverse in children (6-11 years) receiving bilastine 10 mg or placebo.Conclusion: Pharmacokinetic and safety analyses in children aged 6-11 years support the suitability of the pediatric dose of bilastine 10 mg and confirm that the safety profiles of bilastine and placebo are similar.What is Known:• Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults (20 mg/day) and children aged ≥ 6 years (10 mg/day).• An ontogenic model based on adult data and pharmacokinetic/pharmacodynamic simulations supported the selection of a bilastine dose of 10 mg/day in children aged 2-11 years. Bilastine 10 mg/day was shown to have a safety profile similar to that of placebo in a large phase III randomized clinical trial in children aged 2-11 years.What is New:• As bilastine is approved in Europe for children aged ≥6 years, the current study reports the results of two post hoc analyses of pharmacokinetic and safety data in children aged 6-11 years.• Analysis of pharmacokinetic and safety data in children aged 6-11 years supports the suitability of the pediatric dose of bilastine 10 mg and confirms that its safety profile is similar to that of placebo. [ABSTRACT FROM AUTHOR]

Background and Objective: Bilastine is a non-sedating H1 antihistamine indicated for the treatment of allergic rhinoconjunctivitis and urticaria. The aim of this trial was to assess the bioequivalence of three novel pediatric oral formulations of bilastine. Methods: An open label, randomized, four-treatment-period, four-sequence, crossover, single-center study was conducted in 23 healthy volunteers. Each subject received four single doses of bilastine under fasting conditions: a 10-mg orodispersible tablet (DT1), a 10-mg oral solution (SOL), a 10-mg orodispersible tablet without water (DT2dry), and a 10-mg orodispersible tablet with water (DT2water, reference formulation). Blood samples were collected during 72 h with a washout period of at least 7 days. Bilastine maximum plasma concentration (Cmax) and area under the plasma concentration–time curve between 0 to t time (AUC0−t) were calculated to assess bioequivalence. Tolerability was evaluated throughout the study. Results: The three oral pediatric formulations tested were bioequivalent to the reference formulation as determined by the ratio test/reference of the geometric mean and their 90% confidence intervals (between 0.80 and 1.25) for the Cmax, AUC0−t and AUC0−∞. Bilastine was well tolerated when administered indistinctly as an orodispersible tablet or as an oral solution. Conclusion: The three oral pediatric formulations tested were found to be bioequivalent to the reference formulation. All formulations were well tolerated. Trial registration: Spanish Clinical Studies Registry (REEC) number 2014-000786-41. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown. Here we found that chronic atypical antipsychotics downregulated the transcription of metabotropic glutamate 2 receptor (mGlu2, also known as Grm2), an effect that was associated with decreased histone acetylation at its promoter in mouse and human frontal cortex. This epigenetic change occurred in concert with a serotonin 5-HT2A receptor-dependent upregulation and increased binding of HDAC2 to the mGlu2 promoter. Virally mediated overexpression of HDAC2 in frontal cortex decreased mGlu2 transcription and its electrophysiological properties, thereby increasing psychosis-like behavior. Conversely, HDAC inhibitors prevented the repressive histone modifications induced at the mGlu2 promoter by atypical antipsychotics, and augmented their therapeutic-like effects. These observations support the view of HDAC2 as a promising new target for schizophrenia treatment. [ABSTRACT FROM AUTHOR]