Pharmacokinetics and safety of bilastine in children aged 6 to 11 years with allergic rhinoconjunctivitis or chronic urticaria.

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 (C) and area under the plasma concentration curve (AUC) data were compared with adult pharmacokinetic data from seven clinical studies (bilastine 20 mg/day).

Bioequivalence Evaluation of Three Pediatric Oral Formulations of Bilastine in Healthy Subjects: Results from a Randomized, Open Label, Crossover Study.

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.

Efficacy and safety of bilastine in reducing pruritus in patients with chronic spontaneous urticaria and other skin diseases: an exploratory study.

To evaluate the efficacy/safety of bilastine in pruritus relief in patients with chronic spontaneous urticaria (CSU) or other pruritic skin diseases. In this multicenter, open-label, exploratory study (EudraCT No.: 2016-001505-17), 115 adults with CSU ( = 34), eczema/dermatitis ( = 30), prurigo ( = 25) or cutaneous pruritus ( = 26), received bilastine 20 mg once daily for 8 weeks, or in non-responder patients (<30% improvement in pruritus score at week 2), 40 mg/day from week 2.

Model-informed pediatric development applied to bilastine: Analysis of the clinical PK data and confirmation of the dose selected for the target population.

Bilastine is a non-sedating second-generation H antihistamine approved for treatment of allergic rhinoconjunctivitis (AR) and urticaria (U) in adults at the oral (p.o.) dose of 20 mg once daily (OD).

The long duration of action of the second generation antihistamine bilastine coincides with its long residence time at the histamine H receptor.

Drug-target binding kinetics has recently attracted considerable interest in view of the potential predictive power for in vivo drug efficacy. The recently introduced antihistamine bilastine has a long duration of in vivo drug action, which outlasts pharmacological active bilastine concentrations in blood. To provide a molecular basis for the long duration of action, we explored the kinetics of bilastine binding to the human histamine H receptor using [H]mepyramine binding studies and compared its pharmacodynamics properties to the reference compounds fexofenadine and diphenhydramine, which have a long (60 ± 20 min) and short (0.

Open-label safety assessment of bilastine in elderly patients with allergic rhinoconjunctivitis and/or urticaria.

Background: Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo.

Objective: As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed.

Bilastine in allergic rhinoconjunctivitis and urticaria: a practical approach to treatment decisions based on queries received by the medical information department.

Background: Bilastine is a safe and effective commonly prescribed non-sedating H-antihistamine approved for symptomatic treatment in patients with allergic disorders such as rhinoconjunctivitis and urticaria. It was evaluated in many patients throughout the clinical development required for its approval, but clinical trials generally exclude many patients who will benefit in everyday clinical practice (especially those with coexisting diseases and/or being treated with concomitant drugs). Following its introduction into clinical practice, the Medical Information Specialists at Faes Farma have received many practical queries regarding the optimal use of bilastine in different circumstances.

Comparative efficacy of bilastine, desloratadine and rupatadine in the suppression of wheal and flare response induced by intradermal histamine in healthy volunteers.

Objective: To compare the peripheral antihistaminic activity of bilastine, rupatadine and desloratadine in inhibiting the histamine-induced wheal and flare (W&F) response.

Research Design And Methods: Twenty-four healthy volunteers aged 18-40 years participated in this crossover, randomized, double-blind, placebo-controlled clinical study. Subjects received single doses of bilastine 20 mg, desloratadine 5 mg, rupatadine 10 mg and placebo.

Cognitive Performance Effects of Bilastine 20 mg During 6 Hours at 8000 ft Cabin Altitude.

Introduction: Bilastine is a new oral, second generation antihistamine used in the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It is considered a nonsedating antihistamine and might be recommended for use in pilots, pending research on the effects on flying-related performance under hypobaric conditions that prevail in an airliner. We assessed the effects of a single dose of bilastine 20 mg on alertness and complex task performance of healthy volunteers in a hypobaric chamber at 75.

Bilastine: a new antihistamine with an optimal benefit-to-risk ratio for safety during driving.

Introduction: Rational selection of a second-generation H1-antihistamine requires efficacy and safety considerations, particularly regarding central nervous system (CNS) effects (cognitive and psychomotor function), potential for driving impairment, minimal sedative effects and a lack of interactions. This review evaluates the key safety features of the non-sedating antihistamine, bilastine, during driving and in preventing road traffic accidents.

Areas Covered: Among the second-generation H1-antihistamines, sedative effects which can affect cognitive and psychomotor performance, and possibly driving ability, may not be similar.

Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers.

Aim: A close correlation exists between positron emission tomography (PET)-determined histamine H1 -receptor occupancy (H1 RO) and the incidence of sedation. Antihistamines with H1 RO <20% are classified as non-sedating. The objective was to compare the H1 RO of bilastine, a second generation antihistamine, with that of hydroxyzine.

Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4 formation.

A set of 25 derivatives of 3-[1-(6-substituted-pyridazin-3-yl)-5-(4-substituted-phenyl)-1H-pyrazol-3-yl]propanoic acids has been synthesized and evaluated for their in vitro cyclooxygenase-1/2 (COX-1/ 2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes as well as for their 5-lipoxygenase (5-LO)-mediated LTB4 formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes (PMNL). Among the synthesized compounds, especially 4g showed COX-1 (IC50 = 1.5 microM) and COX-2 (IC50 = 1.

Synthesis, biological evaluation, and docking studies of novel heterocyclic diaryl compounds as selective COX-2 inhibitors.

Three novel series of diaryl heterocyclic derivatives bearing the 2-oxo-5H-furan, 2-oxo-3H-1,3-oxazole, and 1H-pyrazole moieties as the central heterocyclic ring were synthesized and their in vitro inhibitory activities on COX-1 and COX-2 isoforms were evaluated using a purified enzyme assay. The 2-oxo-5H-furan derivative 6b was identified as potent COX inhibitor with selectivity toward COX-1 (COX-1 IC(50)=0.061 microM and COX-2 IC(50)=0.

Synthesis and biological evaluation of 4,5-diphenyloxazolone derivatives on route towards selective COX-2 inhibitors.

A series of 3-unsubstituted/substituted-4,5-diphenyl-2-oxo-3H-1,3-oxazole derivatives were prepared as selective cyclooxygenase-2 (COX-2) inhibitors. Among the synthesized compounds, 4-(4-phenyl-3-methyl-2-oxo-3H-1,3-oxazol-5-yl)benzensulfonamide (compound 6) showed selective COX-2 inhibition with a selectivity index of >50 (IC(50)COX-1=>100 microm, IC(50)COX-2=2 microm) in purified enzyme (PE) assay. Compound 6 also exhibited selective COX-2 inhibition in human whole blood assay.

Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors.

New series of 2-(4-methylsulfonylphenyl) and 2-(4-sulfamoylphenyl)pyrimidines were synthesized and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). COX-1 and COX-2 inhibitory activity of these compounds was determined using purified enzyme (PE) and human whole blood (HWB) assays. Extensive structure-activity relationship (SAR) work was carried out within these series, and a wide number of potent and specific COX-2 inhibitors were identified (HWB COX-2 IC(50)=2.

Reversal of learned helplessness by selective serotonin reuptake inhibitors in rats is not dependent on 5-HT availability.

Serotonin (5-HT) and 5-HT(1A) receptors have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, particularly in the case of selective serotonin reuptake inhibitors (SSRIs). In the rat learned helplessness (LH) paradigm, a valid animal model of human depression, repeated treatment with the 5-HT(1A) receptor agonist 8-OH-DPAT (0.125 and 0.

Design, syntheses, biological evaluation, and docking studies of 2-substituted 5-methylsulfonyl-1-phenyl-1H-indoles: potent and selective in vitro cyclooxygenase-2 inhibitors.

Four series of 5-methylsulfonyl-1-phenyl-1H-indole-2-carboxylic acid alkyl esters (family A), -2-carbonitriles (family B), -2-carboxamides (family C), and 2-benzoyl-5-methylsulfonyl-1-phenyl-1H-indoles (family D) were prepared and evaluated for their ability to inhibit purified cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1). Family D compounds have the best COX-1/COX-2 inhibition ratios and potencies. According to docking studies, these molecules appear to bind the COX-2 binding site differently than indomethacin, with the insertion of the substituent at the 2-position in the hydrophobic pocket of the enzyme and the 1-position phenyl ring in the trifluoromethyl zone.

In vivo pharmacological characterisation of bilastine, a potent and selective histamine H1 receptor antagonist.

Objective: We set out to establish the in vivo histamine H(1) receptor antagonistic (antihistaminic) and antiallergic properties of bilastine.

Methods: In vivo antihistaminic activity experiments consisted of measurement of: inhibition of increase in capillary permeability and reduction in microvascular extravasation and bronchospasm in rats and guinea pigs induced by histamine and other inflammatory mediators; and protection against lethality induced by histamine and other inflammatory mediators in rats. In vivo antiallergic activity experiments consisted of measurement of passive and active cutaneous anaphylactic reactions as well as type III and type IV allergic reactions in sensitised rodents.

In vitro and in vivo characterization of F-97013-GD, a partial 5-HT1A agonist with antipsychotic- and antiparkinsonian-like properties.

In order to better define the role of 5-HT(1A) receptors in the modulation of extrapyramidal motor functions, we investigated the effect of 5-HT(1A) agonists on tacrine-induced tremulous jaw movements (TJM) in rats, a putative model of parkinsonian tremor. Acute injection of 5-HT(1A) agonists 8-OH-DPAT and buspirone dose-dependently counteracted the tacrine-induced oral movements (ED(50)=0.04 and 1.

Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity.

Objective: This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist.

Design And Methods: In vitro experiments were conducted using a receptor binding screening panel and guinea-pig and rat tissues. Antihistaminic activity was determined using H1 receptor binding studies and in vitro H1 antagonism studies conducted in guinea-pig tissues and human cell lines.

Preclinical pharmacology of F-98214-TA, a novel potent serotonin and norepinephrine uptake inhibitor with antidepressant and anxiolytic properties.

Rationale: Serotonin (5-HT) and norepinephrine (NE) re-uptake inhibitors (SNRIs) have been proposed to have a higher efficacy and/or faster onset of action than previously available antidepressants.

Objectives: We examined in biochemical, electrophysiological and behavioural assays the antidepressant properties of (S)-(-)-4-[(3-fluorophenoxy)-phenyl]methyl-piperidine (F-98214-TA), a compound that displays very high affinity for 5-HT and NE transporters.

Results: F-98214-TA potently inhibited the uptake of both 5-HT and NE into rat brain synaptosomes (IC50 = 1.

Syntheses and binding studies of new [(aryl)(aryloxy)methyl]piperidine derivatives and related compounds as potential antidepressant drugs with high affinity for serotonin (5-HT) and norepinephrine (NE) transporters.

In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT(1A) and 5-HT(2A) receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT(1A) and 5-HT(2A) receptors.

Synthesis and pharmacological characterization of a new benzoxazole derivative as a potent 5-HT3 receptor agonist.

N-(2-Benzoxazol-2-yl-ethyl)-guanidine hydrochloride (10) was synthesized and pharmacologically tested. This compound showed high affinity for the 5-HT(3) receptor (K(i)=0.77 nM) and potently triggered the von Bezold-Jarisch reflex (BJR) in rats with an ED(50)=0.

New 3-benzisothiazolyl and 3-benzisoxazolylpiperazine derivatives with atypical antipsychotic binding profile.

New 3-benzisothiazolyl and 3-benzisoxazolylpiperazine derivatives were synthesised and their 5-HT(1A), 5-HT(2A) and D(2) receptor binding affinities evaluated. The compounds displayed high affinity for the 5-HT(2A) receptor combined with moderate to low 5-HT(1A) and D(2) affinities. Two of them, 18 and 25, have been selected for further pharmacological studies to be evaluated as potential atypical antipsychotics.