Bilastine Research Articles

Multi-component forms of the 2nd generation H1 receptor antagonist drug, Bilastine and its enhanced physicochemical characteristics

Bilastine (BIL) is a novel 2nd generation antihistamine medication is used to treat symptoms of chronic urticaria and allergic rhinitis. However, its poor solubility limits its therapeutic efficacy. In order to enhance the physicochemical characteristics of BIL, various molecular adducts of BIL (Salt, hydrate and co-crystal) were discovered in this study using two distinct salt-formers: Terephthalic acid (TA), 2,4-Dihydroxybenzoic acid (2,4-DHBA), and three nutraceuticals (Vanillic Acid (VA), Hydroquinone (HQN) and Hippuric acid (HA)). Various analytical methods were used to examine the synthesised adducts, including Powder X-Ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), and thermal analysis (Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC)). Single-crystal X-ray diffraction (SCXRD) studies avowed that the architectures of the molecular adducts are maintained in the solid state by an array of strong (N+H⋯O−, NH⋯O, OH⋯O) and weak (CH⋯O) hydrogen bonds. Additionally, a solubility test was performed to establish the in vitro release characteristics of newly synthesised BIL adducts and it observed that most of the molecular adducts exhibit higher rates of dissolution in comparison to pure BIL; in particular, BIL.TA.HYD showed the highest solubility and the fastest rate of dissolution. Moreover, experiments on flux permeability and diffusion demonstrated that the BIL.TA.HYD and BIL.VA salts had strong permeability and a high diffusion rate. In addition, the synthesized adduct’s stability was assessed at 25 °C and 90 % ± 5 % relative humidity, and it was found that all the molecular salts were stable and did not undergo any phase changes or dissociation. The foregoing result leads us to believe that the newly synthesized molecular adducts’ increased permeability and solubility will be advantageous for the creation of novel BIL formulations.

Bioavailability of Bilastine Oral Self-nanoemulsion: Comparative Study with Commercial Formula in Rats

Background: Bilastine (BL) is a novel non-sedating second-generation antihistamine, and its bioavailability is about 60%. Objective: To compare the bioavailability of prepared oral self-nanoemulsions of BL (BL-SNE) with that of pure BL and marketed tablets. Methods: Four groups of Wistar rats were used in this study, each with six rats weighing between 200 and 250 g. They were treated orally using a a gavage tube. The groups were fed either with conventional tablets ("Alerbix®") after being ground and dispersed with deionized water (DIW), treated with BL-SNE or fed with pure BL powder suspension. The fourth group did not receive any medication. The concentration of BL in the rat’s plasma was measured using HPLC. We used Trandolapril as an an internal standard. Results: The bioavailability results for the the prepared formula, tablet, and pure BL were 24289.91 ng/ml, 0.75 h, 12.81, 97844.7 ng.h/ml, and 98732.9 ng/ml, respectively, for the BL-SNE formula, and 15840.37, 1.0, 13.014, 66140.4, and 67088.3 for the tablets. Meanwhile, the BL suspension demonstrates 10830.12, 1.0 h, 12.96, 59397.12 ng/ml, and 60534.64 ng/ml, respectively. Conclusions: The relative bioavailability of BL-SNE was 1.47 and 1.6 times higher than that of marketed tablets and pure BL, respectively. This indicates an improvement in BL's bioavailability.

Repurposing the antihistamine drug bilastine as an anti-cancer metallic drug entity: synthesis and single-crystal X-ray structure analysis of metal-based bilastine and phen [Co(II), Cu(II) and Zn(II)] tailored anticancer chemotherapeutic agents against resistant cancer cells.

Bilastine (BLA), 2-(4-(2-(4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazole-2-yl)-piperidin-1-yl)-ethyl)-phenyl)-2-methylpropanoic acid, is an active antihistamine drug. With the idea of repurposing drugs from the existing pool of 'active' pharmaceutical ingredients, the therapeutic potency of bilastine as an anticancer agent was investigated via the tailored synthesis of a metal-based anticancer drug formulation of the type [BLA(phen)2M(II)]+·X-, where M = Co, Cu, and Zn and X- = NO3 and ClO4. The synthesized metal-based chemotherapeutics derived from the bilastine drug that acts as a ligand were thoroughly characterized using spectroscopic techniques, namely, UV-vis, FT-IR, and EPR (in the case of 1 and 2); 1H-NMR and 13C-NMR (in the case of 3); ESI-MS and single-crystal X-ray diffraction studies. Comprehensive biological studies (DNA binding, cleavage, and cytotoxic activity) using various biophysical and gel electrophoretic methods were carried out to validate their potential as anticancer agents. The cytotoxic activity of 'therapeutically promising' copper(II)-based drug candidate 2 was evaluated against MCF-7, MBA-MD-231, HeLa, HepG2, and Mia-PaCa-2 cancer cells via an SRB assay, and the results demonstrated 2 as a potent anticancer agent at low nanomolar concentrations against all tested cancer cells, preferably with a much superior anticancer efficacy against human pancreatic cancer cells.

Minor groove binding of antihistamine drug bilastine with calf thymus DNA: A molecular perspective with thermodynamics using experimental and theoretical methods

Molecular recognition which are driven by molecular interactions, is of great interest in drug discovery and targeted drug delivery systems since drugs exhibit their medicinal characteristics when it interacts with target biomolecules. Deoxyribose nucleic acid (DNA) is one of the primary targets for many therapeutic drugs and understanding them at the molecular level is at the forefront of active research. Bilastine (BLS) is one of the commercially available heterocyclic compounds with a benzimidazole nucleus used in the treatment of chronic urticaria and recurrent allergic rhinoconjunctivitis. Various biophysical methods have been employed for the investigation of binding interaction studies between BLS and ct-DNA. UV–Visible and fluorescence spectral studies revealed the interaction between BLS and DNA. UV-Visible studies suggested a binding constant of 1.17±0.2 ×105 M−1. ct-DNA quenched the fluorescence of BLS, and the quenching was found to involve static and dynamic processes. From fluorescence studies, the binding constants were found to be 1.17±0.2×105, 1.65±0.3×105, 2.01±0.3×105 at 298, 303, and 308 K respectively. The interaction was spontaneous in nature with negative ∆G0 values and hydrophobic force was the major driving force with positive ∆H0 (41.54 ±2.5KJ mol−1) and ∆S0 (236.63±3.1J mol−1 K−1) values. Site marker displacement using ethidium bromide, and Hoechst along with viscosity measurement, DNA melting studies confirmed the binding of BLS in the minor-groove of ct-DNA. The minor-groove binding was further supported by studies with KI. Effect of NaCl on the binding revealed an insignificant role of electrostatic interactions. DNA conformational changes were not observed from circular dichroism (CD) studies. Molecular docking studies corroborated the experimental results showing the location of BLS in the minor groove of ct-DNA.

Development of RP-HPLC Method for Simultaneous Determination of Bilastine and Montelukast by Qbd Approach and Its Validation

This study proposes to develop and validate the RP-HPLC method for Bilastine (BIL) and Montelukast (MKT) byQbD to substantiate the RP-HPLC analysis as per ICH validation guidelines. Quality by Design (QbD) allows the accomplishmentof specific unsurprising quality with a predetermined and wanted determination. The simultaneous estimation of BIL and MKTwas performed with C18 (4.6×250 mm, 5-μm particle size) with an LC-10AD pump and PDA detector. The mobile phaseemployed methanol and ammonium acetate buffer pH-3.6 at 85:15 v/v. The flow rate was maintained at 1.0 ml/min, and BIL andMKT were detected at 249nm and 293 nm by UV detector, respectively. The HPLC method provided linear responses found inthe 200–600 μg/ml range. The correlation coefficient was 0.9995 for BIL and 0.9991 for MKT. The LOD and LOQ for BIL andMKT were found to be 0.493, 1.495 μg/ml, and 0.693, 2.100, respectively. The percentage recovery for BIL was 95.33 to 102.06,and for MKT was 96.31 to 104.05, respectively. Calculated information acquired for both the preliminaries roughly coordinateswith the information given by Design expert programming, showing the chromatographic condition's genuineness. Design-Expertversion 10 ("DX10") software has calculated this calculation, setting a composite design of significant parameters. A newselective, rapid, accurate, precise, and sensitive RP-HPLC method was developed and evaluated for the simultaneousdetermination of Bilastine (BIL) and Montelukast sodium (MKT) in a bulk and pharmaceutical dosage form. This method is usefulin the routine quality analysis of combinations of BIL and MKT in bulk and its tablet formulations.

Preparation and Characterization of Bilastine Solid Self-Nanoemulsion using Liquisolid Technique

Background: Supersaturable self-nanoemulsion (S-SNE) is an approach for dealing with low oral bioavailability problems. Bilastine (BL) is a selective H1-antihistamine with a bioavailability of 59%. Objective: To use a liquisolid technique to transform liquid BL S-SNE into powder so that both the S-SNE and liquisolid procedures could be used. Methods: Oleic acid, tween 60, transcutol, and soluplus were used to make the liquid BL-loaded S-SNE that was adsorbed onto the Avicel PH101 and Aerosil 200 admixtures. In vitro dissolution and powder flow characteristics were tested. SEM, DSC, X-ray diffraction, FT-IR analysis, and the average droplet size after dispersion in 0.1N HCl were also utilized to define the best formula's solid state. Results: The best liquid-solid composition, SS-F2, is composed of oleic acid, tween 60, transcutol, soluplus, Avicel 101, and Aerosil 200, with a liquid SNE to Avicel 101 ratio of 1.5:1 and an Avicel 200 to Aerosil 200 ratio of 10:1. SS-F2 displayed good flowability and a significant improvement in drug dissolution, with 100% of the medication released after 60 min compared to 62.27% of the marketed BL tablets. According to the solid-state investigation of formula (SS-F2), BL was shown to be in a solvated state in the solidified nanosystem, with no interactions with the excipient used. It also formed a nanoemulsion with mean droplet sizes of 77.57 nm and a PDI of 0.4178, which was similar to liquid S-SNE. Conclusion: The liquisolid technique is a potential method for solidifying a liquid self-emulsifying system while preserving self-nanoemulsion characteristics and increasing dissolving rate.

STABILITY INDICATING ISOCRATIC HPLC APPROACH TO QUANTIFY MONTELUKAST AND BILASTINE MIX IN BULK AND TABLET FORMULATION

This paper describes an novel, rapid, simple, meticulous and unerring “stability indicating HPLC method” for the assessment of montelukast (MTT) and bilastine (BLE) mix in existence of their degradation products in tablet formulation. Zorbax column XDB-C18 was utilized to separate and analyse MTT and BLE mix. The isocratic mode elution of BLE and MTT mix was made with 0.1M disodium hydrogen phosphate buffer of pH 5.8 (55 % volume ratio) and methanol (45% volume ratio) at 1.0 mL min-1 flow stream. Strong linearity was recorded within the 2.5 - 20 µg mL-1 and 5 - 40 µg mL-1 concentration ranges, with coefficient determination values of 0.9994 and 0.9997, respectively, for MTT and BLE. The recovery percentiles of MTT and BLE were 99.593 % and 99.349 %, respectively. The precision displayed values less than 0.520 % for MTT and less than 0.745 % for BLE. The robustness too was shown in the chromatographic settings by minor variations. The specificity besides stability representing feature was evidenced since the degradation products arisen in stress situations did not interlope in the determination of MTT and BLE mix. Thus, this procedure can be applied for quality regulation analysis of BLE and MTT mix in formulations of tablets.

Combined synthetic and solubility aspects of orotate salt of bilastine

Bilastine (BLA) is an European Medicines Agency approved second-generation antihistamine drug used for the treatment of allergic rhinoconjunctivitis and chronic urticarial. The major disadvantage of Bilastine is its poor aqueous solubility. In the present work, the authors describe the novel salt of BLA with orotic acid (ORA) as a counter ion. ORA is a well-known molecule that exhibits important physiological functions and pharmacological characteristics. The newly formed salt is thoroughly characterized by various spectroscopic and thermal methods. The crystal structure determination by Single-Crystal X-ray Diffraction (SC-XRD) techniques revealed the proton transfer from ORA to piperidine nitrogen of BLA. The melting temperature of the obtained salt was found to be in between the melting of BLA and ORA and the salt is found to be thermally stable until melting based on DSC, TGA, and Hot-stage analysis. FT-IR spectroscopy depicts the formation of salt based on –C = O stretching frequencies of both BLA and ORA. A detailed synthetic method is established for the BLA-ORA salt by employing various approaches in different solvents. The solubility study in purified water (pH=6.5) and 0.1 N HCl (pH=1.2) showed an increase of 4 and 1.2 fold respectively when compared with pure BLA drug.

Stability Indicating Quality by Design-based Development and Validation of Bilastine and Montelukast by Ultra Performance Liquid Chromatography Method

Background: The current work, which was conducted under the quality by design (QbD) paradigm, aims to establish the optimization of ultra-performance liquid chromatography (UPLC) using the design of experiments and response surface theory, such as central composite design (CCD), in order to achieve a good separation and resolution. Methods: The mobile phase was composed of methanol (20:80% v/v) and 0.1% tri fluro amine (TFA) buffer, and chromatographic separation was performed on column phenomenex C18 (50 mm x 4.6 mm x 2.5 m) at a flow rate of 0.4 mL/ min. Montelukast (MON) and bilastine (BIL) were both detected at 260 nm. The suggested method was approved in accordance with International Council for Harmonization (ICH) recommendations. Results: The created technique successfully separates both BIL and MON with a chromatographic resolution of 6.4. The technique was linear for BIL and MON concentrations of 0.5–3.0 μg/mL and 0.25–1.5, respectively, and recovery rates ranged from 99–100%. The drug compounds had distinct degradation products that were identified in stress patterns. Conclusion: For the quantification of BIL and MON in the combination tablet, a precise, simple, reliable, and accurate UPLC method was designed. According to the method validation, it was possible to successfully separate two medicines from their degradants utilizing aQbD techniques.

QUANTIFICATION OF BILASTINE AND MONTELUKAST COMBINATION IN FORMULATIONS UTILIZING LIQUID CHROMATOGRAPHY: STABILITY STUDIES

Objective: We have developed a “stability-indicating RP-HPLC” procedure for the Bilastine (BLS) and montelukast (MTL) analysis of tablets. Methods: The quantification of BLS and MTL combination was implemented utilising a Waters column (C18, 5 μm, 250 mm and 4.6 mm). Isocratic mobile phase had 60% volume KH2PO4 of 0.1M strength with pH 4.2 units and 40% volume methanol at a flow with 1.0 ml/min speed. UV detection at 232 nm was done to examine BLS and MTL. Stability experiments of BLS and MTL under distinctive environments of stress were also performed. Results: The BLS and MTL were eluted at 1.810 min and 2.551 min, respectively. The responses were found to be linear for the concentration ranges of 10-30 µg/ml (BLS) and 5-15 µg/ml (MTL). Percent comparative standard deviance for precision was 0.331% (BLS) and 0.486% (MTL). Percent assay for accuracy was 98.96% (BLS) and 99.00% (MTL). The detection limit and quantitation limit measures for BLS were 0.018 µg/ml and 0.059 µg/ml, respectively, while for MTL it was 0.024 µg/ml and 0.081 µg/ml, respectively. Robustness studies authorized that the method is robust with percent comparative standard deviance of a highest 1.950%. Conclusion: The developed “stability-indicating RP-HPLC” procedure for the BLS and MTL analysis is simple, sensitive, precise, specific and robust, making it appropriate to the assessment of BLS and MTL in a tablet formulation.

Risk and DoE-Based Analytical Failure Mode Effect Analysis (AFMEA) to Simultaneous Estimation of Montelukast Sodium and Bilastine by HPTLC Method Using Enhanced AQbD Approach

The fixed-dose combination (FDC) of montelukast sodium (MLS) and bilastine (BIL) is used for monotherapy in the patient with seasonal allergic rhinoconjuctivitis and asthma. According to the upcoming ICH (International Council for Harmonization) Q14 guideline, the development of the analytical method by the implementation of the Analytical Quality by Design (AQbD) approach based on principles of Quality Risk Management (QRM) and design of experiments (DoE) would be a regulatory requirement for the registration of new drug substance and product in ICH countries. Hence, a robust high-performance thin layer chromatography method has been developed, which was not previously reported for simultaneous estimation of MLS and BIL using risk and DoE-based enhanced AQbD approach. The analytical failure mode effect analysis (AFMEA) was started with the identification of potential analytical failure modes followed by their effect analysis by RPN ranking and filtering method. The DoE-based AFMEA was applied for optimization of high-risk analytical failure modes by central composite design using Design-Expert software. The method operable design ranges and control strategy was set for quality risk management throughout the lifecycle of the developed method. The developed method was validated as per ICH Q2 (R1) guideline. The method was applied for the assay of FDC, and results were found in compliance with the labeled claim.

Chemistry, Pharmacokinetics, Pharmacodynamics and Analytical Methods of Bilastine, a Histamine H1 Receptor Antagonist: An Update.

Bilastine (BIL) is the new generation antihistamine that is used to relieve the symptoms of hayfever, chronic urticaria and other forms of allergic rhinitis. Chemically it is known 2-[4-[2-[4-[1- (2-ethoxyethyl) benzimidazole-2-yl] piperidine-1-yl] ethyl] phenyl]-2-methylpropane acid. The chemical structure of BIL having a hydrophilic carboxylic substituent. BIL has a longer duration of action due to its potent binding affinity to the H1 receptor. This review summarizes the properties, characteristics, chemistry along with analytical and bioanalytical methods used for estimation of BIL from different scientific articles. The literature has demonstrated some methods for quantification of BIL in various sample matrix and pharmaceutical products. Frequently and extensively used antihistaminics are in the clinic practice, a novel, effective, economic and safe analytical methodology is required for routine quality control analysis, bioavailability, and bioequivalence studies. Furthermore, this narrative review summarizes available data on chemistry, pharmacology and analysis of BIL in a different matrix.

Entrapped Transient Chloroform Solvates of Bilastine

The knowledge about the solid forms landscape of Bilastine (BL) has been extended. The crystal structures of two anhydrous forms have been determined, and the relative thermodynamic stability among the three known anhydrous polymorphs has been established. Moreover, three chloroform solvates with variable stoichiometry have been identified and characterized, showing that S3CHCl3-H2O and SCHCl3 can be classified as transient solvates which transform into the new chloroform solvate SCHCl3-H2O when removed from the mother liquor. The determination of their crystal structures from combined single crystal/synchrotron X-ray powder diffraction data has allowed the complete characterization of these solvates, being two of them heterosolvates (S3CHCl3-H2O and SCHCl3-H2O) and SCHCl3 a monosolvate. Moreover, the temperature dependent stability and interrelation pathways among the chloroform solvates and the anhydrous forms of BL have been studied.

Voltammetric Study of the Antihistamine Drug Bilastine: Anodic Characterization and Quantification Using a Reusable MWCNTs Modified Screen Printed Carbon Electrode

AbstractThe anodic behaviour and the electroanalytical quantification of the second‐generation antihistamine bilastine (BIL) were investigated for the first time. A multi‐walled carbon nanotubes (MWCNTs) film‐coated screen printed carbon electrode (SPCE), as well as cyclic (CV) and linear sweep (LSV) voltammetry, were used for that purpose. The results showed that BIL undergoes an irreversible two‐electron oxidation process at the MWCNTs‐SPCE sensor. It was also found that the sensor can be reused after a simple and rapid reconditioning procedure. The proposed method was applied to the quantification of BIL in pharmaceutical formulations and spiked urine samples, and good recoveries were obtained.

Advanced Derivative Spectroscopic Method for Estimation of Montelukast and Bilastine in Their Tablet Dosage Form

The present work aims to develop and validate the advanced derivative spectroscopic method for estimation of Montelukast (MON) and Bilastine (BIL) in their tablet dosage form. This tablet dosage form is used for anti-asthmatic and allergic rhinitis. The developed method can be applied for simultaneous estimation of Montelukast and Bilastine in their combined dosage form. For this advanced derivative method, the absorbance at 226.8 nm (ZCP of Montelukast) and 326.4nm (ZCP of Bilastine) was used to estimate Montelukast and Bilastine, respectively. The developed method is validated by ICH Q2R1 guidelines with validation parameters like linearity, LOD, LOQ, accuracy, precision, robustness, ruggedness and assay were performed using this guideline. The method was found to be linear in the concentration range of 2-14 µg/mL for Montelukast (R2 = 0.999) and 4–28 µg/mL for Bilastine (R2 =0.9997). LOD and LOQ found 0.1216 and 0.3686 for MON, and 0.3406 and 1.0320 for BIL. The precision study wasa carried out by comparing on 3 different concentrations and the result of their %RSD was is less than 2%. Robustness study carried out by the change in scanning speed and change in methanol manufacturer and Ruggedness study carried out by different analyst. Assay study was performed using tablet formulation. The developed method was utilized for simultaneous estimation of Montelukast and Bilastine for its tablet dosage form.

Development and Validation of Reverse Phase High Performance Liquid Chromatography Method for In-vitro Dissolution Testing of Bilastine and Montelukast Sodium Tablets

The objective of this experimental work is to develop and validate a reverse-phase high-performance liquid chromatographic (RP-HPLC) method, which is capable of quantitative estimation of Bilastine (BLS) and Montelukast (MTK) content present in dissolution media accurately and precisely. A simple, fast, specific, rugged, and reproducible analytical method was developed and validated on a Shimadzu Highperformance liquid chromatography (HPLC) system. A Hypersil BDS C18-Column (100 mm x 4.6mm, 3 µm) and 0.1%v/v Triethylamine buffer (pH-3.0): Acetonitrile used as mobile phase with flow rate 1.0 mL/min in gradient mode. The column oven temperature and sample cooler temperature were set to 40°C and 25°C, respectively. The injection volume was 10 µL, and chromatograms were recorded at 220 nm. The run time for 1 sample analysis was 13 minutes. The optimized conditions for dissolution testing include USP type-II apparatus at 75 rpm with 900 mL, 0.5% w/v sodium lauryl sulfate media at 37.0 ± 0.5°C and collected after 45 minutes. Under the above conditions, the retention time (RT) of Bilastine and Montelukast was 1.84 and 7.23 minutes, respectively, without any interference of dissolution media or any other degradant at the RT of both drugs. The calibration curve was linear with R2 value of 0.99984 and 0.99988 for BLS and MTK, respectively. The sample was found stable in dissolution media beyond 12 hours. The analytical method was validated as per International Council for Harmonisation (ICH) guidelines with respect to specificity, precision, linearity, accuracy, stability in aqueous solution, and robustness. The proposed method was found useful for the routine analysis of dissolution samples for quality control purposes.

Therapeutic effect of bilastine in Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber)

BackgroundEnvironmental exposure chambers have been used to expose subjects to aeroallergens to investigate the efficacy of prophylactic treatment with symptomatic agents in Japan. We first examined the therapeutic effect of bilastine (BIL), a novel non-sedative second-generation H1-antihistamine, in subjects with Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber). MethodsThis was a randomized, double-blind, four-way crossover, placebo- and active-controlled phase II study (trial registration number JapicCTI-132213). Subjects were exposed to cedar pollen (8000 grains/m3) for 2 h on Day −1 and 4 h each on Day 1 and 2. BIL 10 or 20 mg, placebo, or fexofenadine hydrochloride (FEX) 60 mg was administered orally 1 h after the start of pollen exposure on Day 1. Placebo or FEX was administered 12 h after the first dosing. The primary efficacy endpoint was the sum of total nasal symptom score (TNSS) from 0 to 3 h after the Day 1 dosing. ResultsWe enrolled 136 subjects and the sum of TNSS on Day 1 of the three active treatments was significantly lower than that of placebo and was maintained up to 26 h after the first dosing (Day 2). The sum of TNSS or sneezing score on Day 1 after BIL 20 mg was more significantly decreased than after FEX. Moreover, BIL showed a faster onset of action than FEX. ConclusionsWe demonstrated the efficacy, rapid onset, and long duration of action of BIL in subjects with Japanese cedar pollinosis exposed to cedar pollen using the OHIO Chamber.

Bilastine for the treatment of urticaria

Bilastine,a newly registered H1-antihistamine,can be orally administrated to treat allergic rhinitis and urticaria.The absorption of bilastine is fast,but it slows when taken with food or fruit juice.Data have confirmed that bilastine has a higher affinity for H1 histamine receptors than for the other receptors,and can reduce the levels of histamine and cytokines.For histamine-induced cutaneous wheal and flare reactions,bilastine 20 mg shows equivalent inhibitory effect with a probably faster onset of action compared with cetirizine 10 mg.With no anticholinergic effect,bilastine dose not impair driving ability.In addition,bilastine has a good tolerability profile with no sedative side effects,no cardiac toxicity,and no hepatic toxicity,which will make it have a broader prospect for clinical application in the future. Key words: Urticaria; Histamine H1 antagonists; Bilastine

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

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.