piperidines and bilastine

Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent.. We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria.. We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software.. We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo.. Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.

Topics: Benzimidazoles; Chronic Urticaria; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic; Urticaria

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.

Topics: Benzimidazoles; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic

Topics: Adolescent; Adult; Benzimidazoles; Child; Drug Interactions; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Quality of Life; Rhinitis, Allergic; Urticaria; Young Adult

Introduction: Allergic conditions frequently require treatment with antihistamines. First-generation antihistamines can potentially interfere with restful sleep, cause “morning after” effects, impair learning and memory, and reduce work efficiency. Second-generation antihistamines, such as bilastine, have been demonstrated to decrease allergy symptoms effectively without causing night-time sleep disturbances and related adverse events.\ \ Method: A real-world case project was developed to help optimize patient care by recognizing the role bilastine can play for allergic conditions where antihistamine treatment is needed. The presented real-world patient cases conducted by the panel members are supported with evidence from the literature, where available. Any discussion concerning off-label use should be considered an expert opinion only.\ \ Results: The real-world cases presented here used bilastine in conditions such as perennial and seasonal allergic rhinitis, chronic urticaria, as well as urticarial vasculitis and pruritus associated with inflammatory skin conditions. The treated patients were between 9 and 76-years old providing information on a full spectrum of patients that require treatment with antihistamines.\ \ Conclusions: The presented real-world cases using the second-generation antihistamine, bilastine, demonstrated favorable outcomes for the treated patients. While effectively relieving symptoms, the antihistamine was reported to be safe and well-tolerated.\ \ J Drugs Dermatol. 2020;19(2)145-154. doi:10.36849/JDD.2020.4835

Topics: Adolescent; Adult; Aged; Benzimidazoles; Child; Histamine Antagonists; Humans; Hypersensitivity; Middle Aged; Piperidines; Urticaria; Young Adult

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.. Among the second-generation H1-antihistamines, sedative effects which can affect cognitive and psychomotor performance, and possibly driving ability, may not be similar. Bilastine is absorbed rapidly, undergoes no hepatic metabolism or cytochrome P450 interaction (minimal drug-drug interaction potential), and is a substrate for P-glycoprotein (limiting CNS entry). Positron emission tomography showed that, compared with other second-generation H1-antihistamines, bilastine has the lowest cerebral histamine H1-receptor occupancy. Bilastine 20 mg once daily (therapeutic dose) is non-sedating, does not enhance the effects of alcohol or CNS sedatives, does not impair driving performance and has at least similar efficacy as other second-generation H1-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria.. Current evidence shows that bilastine has an optimal benefit-to-risk ratio, meeting all conditions for contributing to safety in drivers who need antihistamines, and hence for being considered as an antihistamine of choice for drivers.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Automobile Driving; Benzimidazoles; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines

Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Benzimidazoles; Butyrophenones; Cyproheptadine; Fluticasone; Histamine H1 Antagonists; Humans; Omalizumab; Phthalazines; Piperidines; Pregnenediones; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Urticaria is a highly prevalent disease among people. First-choice treatment continues to be centred on the second-generation H1 antihistamines, including a wide group of drugs with a better therapeutic index (or risk:benefit ratio) than the classic ones, even in the high, off-label dosage occasionally required in chronic urticaria. Bilastine is a newly registered H1-antihistamine for treatment of allergic rhinoconjunctivitis and urticaria. With established antihistaminic and antiallergic properties, it is widely reviewed in the medical literature; however, to our knowledge, a specific review of bilastine's role in the treatment of urticaria was lacking.. This article reviews the medical literature on the effectiveness and safety of bilastine in urticarial syndromes, either spontaneous or inducible, by means of a Medline search from 1990 to present, completed with some nonpublished data provided by the manufacturer.. Once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life in chronic urticaria, with at least comparable efficacy to levocetirizine. As far as studies in healthy volunteers, clinical assays, and recent clinical experience can establish, bilastine's safety profile is adequate, appearing to be entirely free from cardiovascular effects, and not impairing psychomotor performance or actual driving, even at twice the therapeutic dose.

Topics: Animals; Benzimidazoles; Histamine Antagonists; Humans; Piperidines; Treatment Outcome; Urticaria

The year 2012 has seen relevant changes in Polish pharmaceutical legislation and drug reimbursement, among others limiting the reimbursement solely to indications stated in the Summaries of Product Characteristics (SPCs). A discrepancy with expert recommendations became apparent. The aim of this study was to analyze discordances between up-to-date expert recommendations, the SPCs in force, and the evidence for the effectiveness of recommended drugs in urticaria. Guidelines for the treatment of urticaria issued by Polish and international expert bodies were analyzed, along with the SPCs. A systematic review of clinical trials of recommended drugs was carried out. Of drugs recommended by the experts, 203 were authorized in Poland for urticaria treatment, including 167 oral preparations of second-generation antihistamines (SGAH, 8 active substances), 29 oral preparations of first-generation antihistamines (6 substances), 4 preparations of systemic glucocorticosteroids (2), 2 topical glucocorticosteroid preparations (2) and one combined preparation of human immunoglobulin with histamine. Among products both recommended by experts and licensed for the treatment of urticaria in Poland, high or moderate-level of evidence of effectiveness was available for 7 active substances (bilastine, cetirizine, desloratadine, fexofenadine, loratadine, levocetirizine, rupatadine). Nevertheless, 39% of SGAH available in Poland (66 preparations of cetirizine, emedastine, levocetirizine, loratadine or fexofenadine) were registered exclusively for "chronic idiopathic urticaria" - a diagnosis inconsistent with the current state of medical knowledge. We conclude that there exist considerable discrepancies between expert recommendations for the pharmacotherapy of urticaria, the licensed use of drugs as defined in Summaries of Product Characteristics and scientific evidence for their effectiveness.

Topics: Administration, Oral; Administration, Topical; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Glucocorticoids; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Poland; Practice Guidelines as Topic; Terfenadine; Treatment Outcome; Urticaria

Currently available second-generation H1-antihistamines include a wide group of drugs with a better therapeutic index (or risk-benefit ratio) than the classic antihistamines, although their properties and safety profiles may differ. Bilastine is a newly registered H1-antihistamine for the oral treatment of allergic rhinitis and urticaria, with established antihistaminic and antiallergic properties. Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical assays and clinical experience can establish, bilastine's safety profile is satisfactory, since it lacks anticholinergic effects, does not impair psychomotor performance or actual driving, and appears to be entirely free from cardiovascular effects.

Topics: Automobile Driving; Benzimidazoles; Cardiovascular Diseases; Clinical Trials as Topic; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal; Urticaria

The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines development group examined the properties of oral H(1)-antihistamines and made proposals about an 'optimal' drug. Several criteria should be met by oral H(1)-antihistamines in terms of their pharmacological, and clinical efficacy and safety profiles.. Bilastine, a new H(1)-antihistamine, has been approved in 28 European countries for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. To determine its potential place in therapy in the treatment of allergic rhinitis, this manuscript examines whether bilastine meets the criteria defined in the European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for oral H(1)-antihistamines.. The optimal properties of oral H(1)-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria.. Bilastine is a potent inhibitor of the histamine H(1) receptor. Data from preclinical studies have confirmed its selectivity for the histamine H(1) receptor over other receptors, and demonstrated antihistaminic properties in vitro and in vivo. Bilastine does not interfere with the cytochrome P450 system and is devoid of cardiac side effects. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. In large pivotal randomized, placebo-controlled trials (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy than placebo and comparable to that of cetirizine and desloratadine. Moreover, bilastine was shown to improve quality of life, an important outcome of RCTs in allergic diseases. There were no significant changes in laboratory tests, electrocardiograms or vital signs. A potential limitation of this assessment of bilastine is that it is a literature-based review and the findings are dependent upon the quality of the published evidence.. Bilastine meets current EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

Topics: Adolescent; Adult; Anti-Allergic Agents; Asthma; Benzimidazoles; Child; Humans; Piperidines; Practice Guidelines as Topic; Rhinitis, Allergic, Perennial

Knowledge of the biotransformation of oral H₁ antihistamines is clinically important because it can define their pharmacokinetic profile through possible effects on absorption (i.e., first-pass metabolism) and elimination. Further, clinically significant interactions with inhibitors of cytochrome P450 (CYP) have previously been reported for drugs of this therapeutic group, such as terfenadine and astemizole, indicating the possibility of drug-drug interactions involving agents that share the same metabolic pathway. The aim of this article was to review the preclinical testing of a new antihistamine (i.e., bilastine) in terms of its biotransformation in various animal species, including humans, and to evaluate its potential for possible drug-drug interactions involving the CYP system. A wide array of preclinical experiments were reviewed, all of which demonstrated that bilastine undergoes minimal metabolism in all species tested to date, including humans. Further, bilastine did not interact significantly, either as an inhibitor or inducer, with the CYP enzyme system, suggesting a low propensity for involvement in drug-drug interactions. These characteristics demonstrate the potential for bilastine to be a good choice for allergic patients receiving treatment for other concomitant diseases, including those with renal or hepatic dysfunction.

Topics: Animals; Benzimidazoles; Biotransformation; Drug Evaluation, Preclinical; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Species Specificity

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Topics: Administration, Oral; Animals; Benzimidazoles; Drug Evaluation, Preclinical; Female; Fetal Development; Histamine H1 Antagonists, Non-Sedating; Male; No-Observed-Adverse-Effect Level; Piperidines; Pregnancy; Sex Characteristics; Toxicity Tests

Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials.

Topics: Area Under Curve; Benzimidazoles; Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Urticaria

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Topics: Animals; Automobile Driving; Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria; Wakefulness

Bilastine is a potent inhibitor of the histamine H1 receptor. It was recently approved in 28 countries of the European Union for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. Data from preclinical studies confirmed its selectivity for the histamine H1 receptor over other receptors, and demonstrated antihistaminic and antiallergic properties in vivo. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. Bilastine has demonstrated a good safety profile, without serious adverse effects or antimuscarinic effects in clinical trials. There were no significant changes in laboratory tests, electrocardiograms or vital signs. In clinical studies, oral treatment with bilastine 20 mg once daily improved allergic rhinitis with greater efficacy than placebo and comparable to cetirizine and desloratadine. Bilastine 20 mg was more effective than placebo and equivalent to levocetirizine in chronic urticaria, relieving symptoms, improving quality of life and controlling sleep disorders.

Topics: Adult; Animals; Anti-Allergic Agents; Benzimidazoles; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Piperidines; Randomized Controlled Trials as Topic

New H(1)-antihistamines should be effective in relieving the symptoms of allergic disease, should have a rapid onset and long duration of action and should neither cause sedation nor interact with cytochrome P450. A review of bilastine was undertaken to determine whether this newer H(1)-antihistamine meets these requirements.. A Medline search was conducted to identify preclinical and clinical studies of bilastine. This was supplemented with additional articles or abstracts cited in reference lists and/or obtained from online sources and internal reports supplied by Faes Farma. Review of these data indicated that bilastine has high selectivity for H(1)-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood-brain barrier. At the recommended dose of 20 mg, bilastine is non-sedative, does not enhance the effects of alcohol or CNS sedatives, does not impair actual driving tests, shows no cardiotoxicity and has a similar efficacy to other second-generation H(1)-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria.. In view of its favorable pharmacological and clinical characteristics, bilastine is likely to have particular benefit in urticaria for which guidelines recommend increasing the dosage of H(1)-antihistamines up to fourfold if standard dosing is ineffective.

Topics: Animals; Benzimidazoles; Clinical Trials, Phase I as Topic; Histamine H1 Antagonists; Humans; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Urticaria

H1 antihistamines constitute one of the main references for the treatment of allergic rhinitis. Classically, these drugs have been considered effective in controlling sneezing, rhinorrhea and itching, though they have not been regarded as particularly effective in application to nasal obstruction. The most recent studies, involving second-generation H1 antihistamines (desloratadine, fexofenadine, levocetirizine, rupatadine), have shown these drugs to offer effects upon nasal obstruction significantly superior to those of placebo. The present review examines the effect of bilastine, a new, potent and highly specific H1 antihistamine without sedative effects or cardiac toxicity, upon nasal obstruction. The analysis of the data from the different clinical trials indicates that in patients with allergic rhinitis, the effect of bilastine upon nasal obstruction is superior to that of placebo and similar to that of other second-generation H1 antihistamines, manifesting within 24 hours after the start of treatment.

Topics: Benzimidazoles; Clinical Trials as Topic; Histamine H1 Antagonists; Humans; Nasal Obstruction; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Antihistamines have been classifed as first or second generation drugs, according to their pharmacokinetic properties, chemical structure and adverse effects. The adverse effects of antihistamines upon the central nervous system (CNS) depend upon their capacity to cross the blood-brain barrier (BBB) and bind to the central H1 receptors (RH1). This in turn depends on the lipophilicity of the drug molecule, its molecular weight (MW), and affinity for P-glycoprotein (P-gp) (CNS xenobiotic substances extractor protein). First generation antihistamines show scant affinity for P-gp, unlike the second generation molecules which are regarded as P-gp substrates. Histamine in the brain is implicated in many functions (waking-sleep cycle, attention, memory and learning, and the regulation of appetite), with numerous and complex interactions with different types of receptors in different brain areas. Bilastine is a new H1 antihistamine that proves to be effective in treating allergic rhinoconjunctivitis (seasonal and perennial) and urticaria. The imaging studies made, as well as the objective psychomotor tests and subjective assessment of drowsiness, indicate the absence of bilastine action upon the CNS. This fact, and the lack of interaction with benzodiazepines and alcohol, define bilastine as a clinically promising drug with a good safety profile as regards adverse effects upon the CNS.

Topics: Benzimidazoles; Brain; Drug Interactions; Histamine; Histamine H1 Antagonists; Humans; Piperidines

The evaluation of quality of life (QoL) and its modification through therapeutic interventions has become a prioritary concern in recent years and a requirement on the part of regulatory agencies for the authorization of new drugs. In clinical studies of allergic disorders, particularly allergic rhinitis and urticaria, different types of generic questionnaires have been used - especially disease specific instruments such as the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) or skin disease specific tools such as the Dermatology Life Quality Index (DLQI). Throughout its clinical development, bilastine has been shown to be more effective than placebo and at least as effective as cetirizine, levocetirizine, fexofenadine or desloratadine in controlling the symptoms of seasonal allergic rhinitis and chronic urticaria. QoL has been studied as a secondary objective in three allergic rhinitis clinical trials, using the RQLQ, in a total of 2335 patients. Likewise, in chronic urticaria, QoL has been evaluated using the DLQI in a total of 525 patients, versus levocetirizine and placebo. The improvement in the QoL parameters in these studies (RQLQ or DLQI domains) at all times proved proportional to the symptoms improvement. In general, the data obtained relating to changes in QoL are concordant with the mean global visual analog scale (VAS in mm) values and their changes, from the beginning until the end of the treatment period, for all of the trials, for bilastine and all its comparators.

Topics: Benzimidazoles; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Ocular symptoms often accompany allergic rhinitis and can be as or even more bothersome for the patient than the actual nasal symptoms. Ocular manifestations of allergic rhinoconjunctivitis may result from both direct allergen-mediated mast cell stimulation on the surface of the eye and naso-ocular reflexes--histamine being one of the mediators of symptoms onset. An H1 antihistamine would be the first line treatment for allergic conjunctivitis. Since allergic conjunctivitis is always (or almost always) accompanied by nasal symptoms, a second-generation H1 antihistamine administered via oral route is the drug of choice for jointly managing both the nasal and the ocular symptoms--minimizing the impact of the effects inherent to first-generation H, antihistamine, including particularly drowsiness. Bilastine is a new H1 antihistamine with an excellent safety profile, developed for the treatment of allergic rhinoconjunctivitis and urticaria, with potency similar to that of cetirizine and desloratadine, and superior to that of fexofenadine. This new drug has been shown to be effective in controlling the ocular symptoms of allergic rhinoconjunctivitis.

Topics: Benzimidazoles; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Immunoglobulin E; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The following paper reviews the latest news on antihistamines used in the treatment of allergic rhinitis. It describes the new results of investigations on clinical application of H3 and H4 receptors in therapy of allergic diseases as well as the effect of emedastine on histamine-induced tissue remodeling. Contemporary clinical research of these drugs fulfills the requirements of placebo-controlled trials, including the comparison with a reference drug, usually cetirizine. The paper discusses efficacy and safety of a new drug--bilastine, and the possibility to improve clinical outcome by combining antihistamine drugs with inhaled glucocorticosteroids and antileukotrienes. It also presents the studies on high efficacy of nasal antihistamines, which most probably results from their high concentration in inflamed tissue, as well as describes the latest news on safe use of antihistamines, including studies of fexofenadine enantiomers in drug interactions with P-glycoprotein, safety of a new antihistamine medication--rupatadine, and psychostimulating effect of some other antihistamines. The review shows that antihistamines, the most frequently used class of anti-allergy medications, have been constantly improved, which is of significant importance for progress of allergic diseases treatment.

Topics: Administration, Inhalation; Anti-Allergic Agents; Benzimidazoles; Clinical Trials as Topic; Drug Combinations; Glucocorticoids; Histamine Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis.. Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated.. A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed.. All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.

Topics: Adult; Anti-Allergic Agents; Benzimidazoles; Conjunctivitis, Allergic; Double-Blind Method; Humans; Ophthalmic Solutions; Piperidines; Pruritus

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2-<12 years) followed EMA-authorized processes. Pharmacokinetic/pharmacodynamic simulation and modeling and a pharmacokinetic study were conducted to identify and confirm the pediatric dose (10 mg/day). A Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group study was performed to confirm the safety of bilastine 10 mg/day in children. In this article, evidence is reviewed for use of bilastine in children with allergic rhinoconjunctivitis or urticaria. Several cases are presented which demonstrate its role in routine clinical practice.

Topics: Adolescent; Benzimidazoles; Child; Double-Blind Method; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Treatment Outcome; Urticaria

The aim of this study was to compare the pharmacodynamic activity of bilastine administered under fasting and fed conditions in healthy volunteers.. In this randomized, open-label, two-period, crossover study involving 24 healthy subjects, once-daily oral bilastine 20 mg was administered for 4 days under fasting and fed conditions, with a 7-day washout period. Bilastine plasma concentrations were measured for 24 h after the first and fourth doses in each period. Pharmacodynamic activity was assessed by wheal and flare surface inhibition and subjective assessment of itching, after intradermal injection of histamine 5 μg.. When administered under fed versus fasting conditions, exposure to bilastine 20 mg decreased (mean maximum plasma concentration and area under the curve from time 0 to 24 h decreased by 34.27% and 32.72% [day 1], respectively, and 33.08% and 28.87% [day 4]). Despite this, the antihistaminic effect of bilastine 20 mg was not altered by food. On day 1, as assessed by wheal and flare surface inhibition, the maximum effect and duration of action of bilastine did not differ to a significant extent between fasting and fed conditions, with only a short 30-min delay in the onset of wheal inhibition. At steady state (day 4), bilastine's pharmacodynamic effects were not significantly affected under fasting or fed conditions.. The pharmacokinetic interaction of bilastine with food does not imply a significant reduction of its peripheral antihistaminic efficacy. Despite a slight delay in onset of action on the first treatment day, the global clinical efficacy of bilastine is not affected by coadministration with food.

Topics: Area Under Curve; Cross-Over Studies; Food-Drug Interactions; Humans; Piperidines; Urticaria

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.. 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 (C. 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 C. The three oral pediatric formulations tested were found to be bioequivalent to the reference formulation. All formulations were well tolerated.. Spanish Clinical Studies Registry (REEC) number 2014-000786-41.

Topics: Administration, Oral; Adolescent; Adult; Area Under Curve; Benzimidazoles; Cross-Over Studies; Fasting; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Pharmaceutical Solutions; Piperidines; Tablets; Therapeutic Equivalency; Young Adult

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous appearance of wheals, angioedema, or both for > 6 weeks. Continuous treatment with H1-antihistamines is used as a first-line treatment for CSU. However, H1-antihistamine treatment leads to absence of symptoms in less than 50% of patients with CSU. Although Japanese guidelines for the diagnosis and treatment of urticaria recommend an increase in the H1-antihistamine dose or a switch to other H1-antihistamines, there is no evidence supporting a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.. We will conduct a multicenter, open-label, non-inferiority, randomized, parallel, comparison study to determine if the efficacy of bilastine 20 mg is not inferior to that of a twofold H1-antihistamine dose increase in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. This study will be performed at 15 academic hospitals in Japan, and the administration period (increasing the H1-antihistamine dose twofold vs. switching to bilastine 20 mg) will be 7 days. Participants (n = 150) will be randomized to either an increased H1-antihistamine dose or a switch to bilastine 20 mg at a 1:1 ratio. The primary endpoint, mean of the total symptom score of 5-7 days after the intervention, will be evaluated. The secondary objective is to determine if the safety of bilastine 20 mg regarding somnolence is superior to that of a twofold dose increase of H1-antihistamines. This will be measured by a change in the Japanese version of the Epworth Sleepiness Scale from baseline to 7 days after starting the intervention.. This multicenter, open-label, non-inferiority, randomized, parallel, comparison study will be, to our knowledge, the first well-designed clinical study to evaluate the efficacy of a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed doses. This trial will provide evidence of the efficacy and safety of bilastine when treatment is switched in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.. Japan Registry of Clinical Trials (jRCT), jRCTs051180105. Registered on 8 March 2019.

Topics: Adult; Benzimidazoles; Chronic Urticaria; Dose-Response Relationship, Drug; Drug Substitution; Equivalence Trials as Topic; Histamine H1 Antagonists; Humans; Japan; Multicenter Studies as Topic; Piperidines; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

Chronic spontaneous urticaria (CSU) is a debilitating condition, adversely affecting the patient's quality of life. Bilastine is a recently introduced, non-sedative H1-antihistamine for its treatment. We wanted to compare the effectiveness, safety, and tolerability of bilastine 20 mg vs levocetirizine 5 mg in moderate-to-severe CSU. We conducted a double-blind, randomized controlled trial with two groups: bilastine 20 mg (n = 31) and levocetirizine 5 mg (n = 27), once daily for 42 days. We included patients (18-65 years), with moderate-to-severe CSU. UAS7, VAS, and DLQI were used to assess severity of urticaria, global urticaria-induced discomfort and quality of life, respectively. DLQI was assessed at baseline (D0) and end-of-treatment (D42), while UAS7 and VAS were noted at baseline and all follow-up visits. Assessment of UAS7 alteration was our primary objective, while changes in DLQI and VAS were the secondary outcomes. Safety was assessed by recording drug-related adverse events, biochemical investigations, and electrocardiogram, along with tolerability and compliance. Both drugs significantly improved UAS7, DLQI, and VAS at end-of-treatment (D42) compared with baseline (intra-group). At the end-of-treatment, all parameters showed greater improvement with bilastine, but only UAS7 reduction was significant (bilastine > levocetirizine, P = .03). In both the groups, UAS7 and VAS improved significantly D14 onwards, and was maintained throughout the study. Sedation was significantly less with bilastine (P = .04), while neither drug showed any serious adverse-effect. Tolerability of both drugs was similar. Therefore, bilastine was found to be a more effective and less-sedative novel therapy for CSU compared to levocetirizine, with similar effect on quality of life.

Topics: Benzimidazoles; Cetirizine; Chronic Disease; Chronic Urticaria; Double-Blind Method; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Quality of Life; Treatment Outcome; Urticaria

Bilastine is a highly selective, non-sedating antihistamine, indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Available data suggest that bilastine interferes neither with driving ability nor with flying-related performance. However, no data are available on the effect of bilastine on the driving ability in extreme conditions. Here we analyzed the effect of 7 days treatment with 20 mg bilastine in patients with allergic rhinitis and/or chronic urticaria, on psychophysical performance assessed by the Formula One (F1) high-speed simulator-driving test.. This study is a phase IV, interventional, prospective, mono-centric, single arm, open-label trial. Eighteen outpatients affected by allergic rhinitis and/or chronic urticaria, able to perform a preliminary driving test on F1 simulator were considered (V-1). First, the patients had a screening visit to assess their eligibility (V0). Visit 1 (V1), at the end of placebo before bilastine treatment and Visit 2 (V2), at the end of bilastine treatment. The primary variable parameter was the ability to maintain the vehicle in a central position at different speeds (50, 150, and 250 km/h).. Bilastine had a good safety profile and was well tolerated in terms of adverse events, laboratory parameters and vital signs. Bilastine did not have any negative effect on the ability to maintain the requested path, a constant speed as well as on attention and reactivity levels, even in extreme driving conditions.. This study is the first done in patients with allergic rhinitis and/or chronic urticaria using a F1-high speed simulator-driving test evaluating subjects' performance under bilastine treatment.

Topics: Adult; Attention; Automobile Driving; Benzimidazoles; Chronic Disease; Computer Simulation; Dizziness; Female; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Rhinitis, Allergic; Urticaria; Young Adult

Antihistamines are easily accessible and cover the vast majority of the medical therapy of allergic rhinitis. However, their systemic administration may more frequently associate with their well-known side-effect, sedation, which is a serious problem in persons in safety-critical jobs such as aviation. We have a poor understanding whether a non-sedative antihistamine has an impact on vigilance when hypobaric hypoxia occurs during flight.. In this randomized, placebo-controlled, double-blind, cross-over study the effect of 20 mg bilastine was compared to 10 mg cetirizine and to placebo (20 mg pyridoxine) in 33 individuals at ground level and at 4,000 m altitude simulated in hypobaric chamber. Levels of vigilance, ultrashort memory, combined distributive attention, monotony tolerance and peripheral blood oxygen saturation (SpO. Bilastine did not impair the tested abilities in comparison with the control groups either at ground level or hypobaric hypoxia. Administration of cetirizine increased the number of errors at ground level. At the simulated altitude, already impaired results were additionally demonstrated with regards to the distributive attention test.. From the two examined antihistamines, bilastine should be the preferred medication for by individuals who require constant attention and are exposed to hypobaric hypoxia.

Topics: Adult; Altitude; Anti-Allergic Agents; Atmosphere Exposure Chambers; Aviation; Benzimidazoles; Cetirizine; Cognition; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines

A semi-mechanistic approach was applied to predict bilastine PK in children assuming the same PD as described in adults. The model was used to simulate the time evolution of plasma levels and wheal and flare effects after several doses and design an adaptive PK trial in children that was then confirmed using data from the first recruits by comparing observations with model predictions.. PK/PD simulations supported the selection of 10 mg/day in 2 to <12 year olds. Results from the first interim analysis confirmed the model predictions and design hence trial continuation.. The model successfully predicted bilastine PK in pediatrics and optimally assisted the selection of the dose and sampling scheme for the trial in children. The selected dose was considered suitable for younger children and the forthcoming safety study in children aged 2 to <12 years.

Topics: Algorithms; Benzimidazoles; Child; Child, Preschool; Computer Simulation; Drug Dosage Calculations; Histamine H1 Antagonists; Humans; Models, Biological; Piperidines; Software

Bilastine, a novel non-sedating second-generation H. This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13).. A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated.. After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.

Topics: Adult; Asian People; Benzimidazoles; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal; Terfenadine

Environmental 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 H. This 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/m. We 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.. We 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.

Topics: Adult; Benzimidazoles; Cryptomeria; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Seasonal

Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR).. Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements.. Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR.. Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622).

Topics: Adult; Benzimidazoles; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Japan; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Bilastine, a novel non-sedating second-generation H. We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores.. A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated.. Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action.

Topics: Adolescent; Adult; Aged; Benzimidazoles; Chronic Disease; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Phenotype; Piperidines; Quality of Life; Treatment Outcome; Urticaria; Young Adult

To compare the peripheral antihistaminic activity of bilastine, rupatadine and desloratadine in inhibiting the histamine-induced wheal and flare (W&F) response.. 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. W&F responses induced by intradermal injection of histamine 5 μg were evaluated before treatment (basal value) and at 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after treatment. Fifteen minutes after histamine injection, W&F surface areas (cm. The primary outcome measure was the percentage reduction in W&F areas after each active treatment compared with corresponding basal values.. Bilastine induced the greatest inhibition in wheal area and was significantly superior to desloratadine and rupatadine from 1 to 12 hours (both p < .001). Rupatadine and desloratadine were better than placebo without differences between them. Maximum wheal inhibition occurred at 6 hours (bilastine 83%, desloratadine 38%, rupatadine 37%). Onset of action was 1 hour for bilastine and 4 hours for desloratadine and rupatadine. Bilastine was significantly superior to desloratadine and rupatadine for flare inhibition from 1-24 hours (both p < .001) with an onset of action at 30 minutes. Bilastine was significantly better than desloratadine (2-12 hours; at least p < .05) and rupatadine (2-9 hours; at least p < .01) for reducing itching sensation. Neither desloratadine nor rupatadine significantly reduced itching compared to placebo. All active treatments were well tolerated.. Bilastine 20 mg induced significantly greater inhibition of the W&F response compared with desloratadine 5 mg and rupatadine 10 mg throughout the 24 hour study period, and had the fastest onset of action. Only bilastine significantly reduced itching sensation versus placebo.

Topics: Adult; Benzimidazoles; Cross-Over Studies; Cyproheptadine; Double-Blind Method; Female; Healthy Volunteers; Histamine; Histamine Antagonists; Humans; Injections, Intradermal; Loratadine; Male; Piperidines; Skin

A number of second-generation non-sedating antihistamines are used in clinical practices over the world. However, long-term safety and efficacy have not been proved high level evidence based medicine. We have performed an open-label, multicenter, phase III study to evaluate the long-term safety and efficacy of bilastine, a novel non-sedating H

Topics: Adult; Benzimidazoles; Chronic Disease; Eczema; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Japan; Long Term Adverse Effects; Male; Middle Aged; Piperidines; Prurigo; Pruritus; Quality of Life; Severity of Illness Index; Treatment Outcome; Urticaria

Regulations on medicinal products for paediatric use require that pharmacokinetics and safety be characterized specifically in the paediatric population. A previous study established that a 10-mg dose of bilastine in children aged 2 to <12 years provided an equivalent systemic exposure as 20 mg in adults. The current study assessed the safety and tolerability of bilastine 10 mg in children with allergic rhinoconjunctivitis and chronic urticaria.. In this phase III, multicentre, double-blind study, children were randomized to once-daily treatment with bilastine 10-mg oral dispersible table (n = 260) or placebo (n = 249) for 12 weeks. Safety evaluations included treatment-emergent adverse events (TEAEs), laboratory tests, cardiac safety (ECG recordings) and somnolence/sedation using the Pediatric Sleep Questionnaire (PSQ).. The primary hypothesis of non-inferiority between bilastine 10 mg and placebo was demonstrated on the basis of a near-equivalent proportion of children in each treatment arm without TEAEs during 12 weeks' treatment (31.5 vs. 32.5%). No clinically relevant differences between bilastine 10 mg and placebo were observed from baseline to study end for TEAEs or related TEAEs, ECG parameters and PSQ scores. The majority of TEAEs were mild or moderate in intensity. TEAEs led to discontinuation of two patients treated with bilastine 10 mg and one patient treated with placebo.. Bilastine 10 mg had a safety and tolerability profile similar to that of placebo in children aged 2 to <12 years with allergic rhinoconjunctivitis or chronic urticaria.

Topics: Adolescent; Adult; Benzimidazoles; Child; Child, Preschool; Chronic Disease; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Treatment Outcome; Urticaria

Bilastine is a novel second-generation antihistamine for the symptomatic treatment of allergic rhinitis and urticaria. The objective of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of bilastine following single and multiple oral doses in healthy Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared with those reported in Caucasian subjects.. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study, bilastine tablets were administered at single doses of 10, 20, and 50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II).. After single oral doses, maximum plasma concentrations (C. Bilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.

Topics: Adolescent; Adult; Area Under Curve; Benzimidazoles; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Single-Blind Method; Young Adult

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 75.2 kPa (8000 ft/2438 m cabin altitude).. In a randomized, double-blind, crossover study, 24 volunteers received a single dose of bilastine 20 mg, hydroxyzine 50 mg (active control), and placebo. Using the Vigilance and Tracking Task, Multi-Attribute Task Battery, and Stanford Sleepiness Scale, assessments were made before and up to 6 h after intake of the study medication.. Bilastine 20 mg had no impairing effects on sleepiness levels, vigilance, or complex task performance for up to 6 h post-dose. Hydroxyzine 50 mg (active control) was associated with significant sleepiness and impaired performance across this time period, confirming the sensitivity of the tests.. Bilastine 20 mg did not cause sleepiness or impaired performance on tasks related to flying. It is anticipated that a single dose of bilastine 20 mg will not affect flying performance. Bilastine may provide a safe therapeutic alternative for pilots suffering from allergic rhinitis or urticaria. Our findings might also have implications for the treatment of allergic disorders of personnel involved in other safety-sensitive jobs. Valk PJL, Simons R, Jetten AM, Valiente R, Labeaga L. Cognitive performance effects of bilastine 20 mg during 6 hours at 8000 ft cabin altitude. Aerosp Med Hum Perform. 2016; 87(7):622-627.

Topics: Altitude; Benzimidazoles; Cognition; Cross-Over Studies; Double-Blind Method; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Psychomotor Performance; Sleep Stages

The aim of this study was to compare the effects of concomitant administration of alcohol and bilastine versus alcohol alone on the central nervous system.. Twenty-four healthy young volunteers of both sexes participated in a randomized, double-blind, double-dummy, crossover, and positive-controlled and placebo-controlled clinical trials. At 1-week intervals, subjects received six different treatments: (i) placebo; (ii) alcohol 0.8 g/kg alone (ALC); (iii) ALC in combination with: bilastine 20 mg (B20 + A); (iv) bilastine 80 mg (B80 + A); (v) cetirizine 10 mg (CET + A); and (vi) hydroxyzine 25 mg (HYD + A). Psychomotor performance tests (fine motor, finger tapping, nystagmus, critical flicker-fusion frequency, temporal estimation, 'd2' cancellation, and simple reaction time) and subjective self-reports (drunkenness, drowsiness, mental slowness, clumsiness, anger, attentiveness, competence, happiness, hostility, interest, and extroversion) were carried out at baseline and multiple points thereafter.. All active treatments induced a significant psychomotor impairment. The greatest and most lasting impairment was observed with HYD + A followed by B80 + A and CET + A. In contrast, objective measures showed less impairment with B20 + A and ALC, both with a similar magnitude. Self-reports showed a subjective perception of performance impairment in all active treatments.. Concomitant administration of bilastine (at therapeutic dose) and alcohol does not produce greater central nervous system depressant effects than ACL alone.

Topics: Adolescent; Adult; Affect; Alcohol Drinking; Benzimidazoles; Central Nervous System Depressants; Cetirizine; Cross-Over Studies; Double-Blind Method; Drug Interactions; Ethanol; Female; Histamine Antagonists; Humans; Hydroxyzine; Male; Piperidines; Psychomotor Performance; Sex Factors; Young Adult

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.. This randomized, double-blind, crossover study used PET imaging with [(11) C]-doxepin to evaluate H1 RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1 ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated.. The mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P < 0.01; mean difference and 95% CI -0.130 [-0.155, 0.105]). There was no significant difference between bilastine and placebo. Overall H1 RO by bilastine was significantly lower than that by hydroxyzine (mean value -3.92% vs. 53.95%, P < 0.01; mean difference and 95% CI 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine.. A single oral dose of bilastine 20 mg had minimal H1 RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine.

Topics: Adult; Automobile Driving; Benzimidazoles; Brain; Carbon Radioisotopes; Cross-Over Studies; Data Interpretation, Statistical; Double-Blind Method; Healthy Volunteers; Histamine H1 Antagonists; Humans; Hydroxyzine; Male; Piperidines; Positron-Emission Tomography; Protein Binding; Psychomotor Performance; Receptors, Histamine H1

Bilastine (Bilaxten™) is a novel non-sedating H1 receptor antagonist (antihistamine) developed in the dosage form of oral tablets and indicated for the treatment of allergic rhinitis (seasonal and perennial) and urticaria. Several clinical trials have been performed in order to determine the efficacy and safety of bilastine. The aim of this trial was to study the absolute oral bioavailability of bilastine in humans.. Twelve male and female adults were recruited into a single centre for a randomized, single-dose, open-label, controlled two-arm crossover study with a minimum 14-day washout period between the two single doses. Two single doses of bilastine were administered: a 20-mg oral tablet and a 10-mg intravenous formulation. Blood and urine samples were collected between 0 and 72 h post each administration. The clinical trial was carried out under quality assurance and quality control systems with standard operating procedures to ensure that the study was conducted and data generated in compliance with the protocol, Good Clinical Practice standards, International Conference on Harmonisation and other applicable regulations.. Oral bioavailability of bilastine was 60.67 % with a 90 % parametric confidence interval of 53.79-67.56. The maximum bilastine concentration was measured 1.31 h after oral administration. Pharmacokinetic parameters were similar to those observed in previous studies. Tolerance to treatment was good, with no adverse events related to study medication.. The absorption of bilastine after oral administration to healthy subjects was rapid. The absolute oral bioavailability was moderate.

Topics: Administration, Oral; Adolescent; Analysis of Variance; Benzimidazoles; Biological Availability; Cross-Over Studies; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Injections, Intravenous; Intestinal Absorption; Male; Piperidines; Spain; Tablets; Young Adult

Cold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge.. Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds (CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine.. Bilastine 20 mg was highly effective (P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly (P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1-3 h after cold challenge were significantly (P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treatment was well tolerated without evidence of increased sedation with dose escalation.. Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines.

Topics: Administration, Oral; Adult; Aged; Benzimidazoles; Chi-Square Distribution; Cold Temperature; Confidence Intervals; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Risk Assessment; Statistics, Nonparametric; Treatment Outcome; Urticaria; Young Adult

Bilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries.. This study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin.. The study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18-80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m(2)]; (2) mild renal insufficiency (GFR 50-80 mL/min/1.73 m(2)); (3) moderate renal insufficiency (GFR 30-50 mL/min/1.73 m(2)); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m(2)). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics.. There was a clear trend of increasing area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) through the groups 1-4. The mean AUC from time zero to infinity (AUC(∞)) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among groups in median time to reach Cmax (tmax) or in the mean terminal disposition rate constants for bilastine were found. Renal and plasma clearance paralleled GFR. In all groups of renally impaired subjects the corresponding 90 % confidence interval of both AUC(∞) and AUC from time zero to time of last measurable plasma concentration (AUC(last)) were not within the 0.8-1.25 interval, indicating that bioequivalence between groups could not be demonstrated. The majority of bilastine was excreted within the first 12 h, and elimination was essentially complete by 72 h.. An oral dose of bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase in exposure. The oral plasma clearance to renal clearance ratio [(CL(P)/F)/CL(R)] was approximately equal in the different groups, suggesting that renal excretion was the main elimination route for bilastine, and no alternative elimination routes were used even in severe renal insufficiency. Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

Topics: Aged; Aged, 80 and over; Area Under Curve; Benzimidazoles; Drug Evaluation; Female; Glomerular Filtration Rate; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Renal Insufficiency

The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

Topics: Adult; Anti-Allergic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzimidazoles; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Electrocardiography; Female; Half-Life; Histamine H1 Antagonists, Non-Sedating; Humans; Ketoconazole; Male; Metabolic Clearance Rate; Piperidines; Young Adult

Bilastine is a non-sedating second-generation H(1) antihistamine with proven efficacy and safety in the treatment of patients with seasonal allergic rhinitis and urticaria. The objective of this study was to demonstrate the efficacy and safety of bilastine in patients with perennial allergic rhinitis (PAR).. In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients with symptomatic PAR (n = 650) from Argentina, Europe, and South Africa received bilastine 20 mg, cetirizine 10 mg, or placebo once daily for 4 weeks. The primary efficacy outcome was the mean area under the curve (AUC) of reflective total 6-symptom scores (rT6SS) from baseline visit to day 28 (D28). Secondary outcome measures included mean AUC of instantaneous total 6-symptom scores (iT6SS), and mean AUCs of reflective and instantaneous total 4-nasal symptom scores (T4NSS) and total 2-ocular symptom scores (T2OSS) from baseline to D28. An open-label extension phase evaluated the safety of bilastine 20 mg administered to patients (n = 513) for one year.. In the overall population no significant differences in efficacy outcomes were found between active treatments and placebo. On account of the high placebo response in South Africa, a post-hoc analysis was conducted. This analysis demonstrated that statistically significant differences existed between active treatments and placebo in the mean AUC of rT6SS (p < 0.05) and T4NSS (p < 0.02), respectively, from baseline to D28 visit for the intent-to-treat population in patients from Europe and Argentina, whereas the difference was not statistically significant in South Africa. Whether this is related to differences in the demographic or clinical characteristics of South African patients (they had PAR for longer and reported more severe symptoms) and/or the disease management process compared with their European and Argentinean counterparts warrants further investigation.. A post-hoc analysis indicated that bilastine and cetirizine were similarly effective and more effective than placebo during a 4-week treatment period in patients with PAR. In addition, bilastine was shown to be safe and well-tolerated over a 1-year treatment period.. NCT01127620.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Argentina; Benzimidazoles; Cetirizine; Child; Dosage Forms; Double-Blind Method; Drug Administration Schedule; Europe; Female; Humans; Male; Middle Aged; Piperidines; Placebos; Rhinitis, Allergic, Perennial; South Africa; Treatment Outcome; Young Adult

The International Conference of Harmonisation (ICH) E14 guideline for thorough QT studies requires assessing the propensity of new non-antiarrhythmic drugs to affect cardiac repolarization. The present study investigates whether a composite ECG measure of T-wave morphology (Morphology Combination Score [MCS]) can be used together with the heart rate corrected QT interval (QTc) in a fully ICH E14-compliant thorough QT study to exclude clinically relevant repolarization effects of bilastine, a novel antihistamine.. Thirty participants in this crossover study were randomly assigned to receive placebo, moxifloxacin 400 mg, bilastine at therapeutic and supratherapeutic doses (20 and 100 mg) and bilastine 20 mg co-administered with ketoconazole 400 mg. Resting ECGs recorded at 12 nominal time points before and after treatments were used to determine Fridericia corrected QTc (QTcF) and MCS from the T-wave characteristics: asymmetry, flatness and notching.. There were no effects of bilastine monotherapy (20 and 100 mg) on MCS or QTcF at those study times where the bilastine plasma concentrations were highest. MCS changes for bilastine monotherapy did not exceed the normal intrasubject variance of T-wave shapes for triplicate ECG recordings. Maximum QTcF prolongation for bilastine monotherapy was 5 ms or less: 3.8 ms (90% CI 0.3, 7.3 ms) for bilastine 20 mg and 5.0 ms (90% CI 2.0, 8.0 ms) for bilastine 100 mg. There were no indications of bilastine inducing larger repolarization effects on T-wave morphology as compared with the QTcF interval, as evidenced by the similarity of z-score equivalents for placebo-corrected changes in MCS and QTcF values.. This study shows that bilastine, at therapeutic and supratherapeutic dosages, does not induce any effects on T-wave morphology or QTcF. These results confirm the absence of an effect for bilastine on cardiac repolarization.

Topics: Adult; Aza Compounds; Benzimidazoles; Cross-Over Studies; Double-Blind Method; Electrocardiography; Female; Fluoroquinolones; Guidelines as Topic; Histamine Antagonists; Humans; Long QT Syndrome; Male; Moxifloxacin; Piperidines; Quinolines; Time Factors; Young Adult

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

Topics: Adult; Automobile Driving; Benzimidazoles; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hydroxyzine; Male; Middle Aged; Piperidines; Psychomotor Performance; Young Adult

Comparison of bilastine and cetirizine in inhibiting skin wheal and flare responses over 24 h.. Twenty-one healthy male volunteers (aged 19-44 years).. Volunteers were randomised to receive single oral doses of 20 or 50 mg bilastine, 10 mg cetirizine or placebo before provocation of wheal and flare responses to 100 mg/ml histamine by skin prick 1.5, 4, 8, 12 and 24 h later.. There were no significant differences between overall inhibitions of wheal or flare by 20 mg bilastine and 10 mg cetirizine. Bilastine was faster in onset than cetirizine, inhibitions of wheal and flare at 1.5 h being 89 ± 3 versus 44 ± 14% (P = 0.011) and 85 ± 4 versus 45 ± 14% (P = 0.016), respectively (Student's t test). At 1.5 h, both wheals and flares were inhibited by >70% in 11/12 volunteers taking bilastine and 3/11 taking cetirizine (P = 0.003, Fisher's exact test). There were no significant differences between the drugs at later times. Bilastine 50 mg had a longer duration of action than bilastine 20 mg.. Both 20 mg bilastine and 10 mg cetirizine are effective and of long duration in reducing histamine-induced wheal and flare responses, the major difference between the two drugs being the more rapid onset of action of bilastine.

Topics: Adult; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Cross-Over Studies; Double-Blind Method; Histamine; Histamine H1 Antagonists; Humans; Male; Piperidines; Skin Tests; Urticaria; Young Adult

Bilastine is a novel nonsedative H(1)-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). The aim of this study was to compare the clinical efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg and placebo in CU patients with moderate-to-severe symptoms.. Overall 525 male and female subjects aged 18-70 years were randomized to receive bilastine 20 mg, levocetirizine 5 mg or placebo, once daily for 28 days, in double-blind manner, in 46 centres across Europe and Argentina. Patients rated symptoms of pruritus, number of wheals, and maximum size of wheals (on predefined scales) as reflective (over past 12 h) symptoms twice daily, for assessment of change from baseline in the total symptoms scores (TSS) over 28 days as the primary efficacy measure. Changes in reflective and instantaneous symptoms scores, Dermatology Life Quality Index (DLQI), and CU-associated discomfort and sleep disturbance were assessed as secondary outcomes. Safety was assessed according to adverse events, laboratory tests and electrocardiograms.. Bilastine reduced patients' mean reflective and instantaneous TSS from baseline to a significantly greater degree than placebo (P < 0.001); from day 2 onwards of treatment. The DLQI, general discomfort, and sleep disruption were also improved significantly in bilastine-treated patients as compared with placebo-treated patients (P < 0.001 for all parameters). Comparison with levocetirizine indicated both treatments to be equally efficacious as well as equally safe and well tolerated as compared with placebo.. Bilastine 20 mg is a novel effective and safe treatment option for the management of CU.

Topics: Adolescent; Adult; Aged; Area Under Curve; Benzimidazoles; Cetirizine; Chronic Disease; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Quality of Life; Urticaria; Young Adult

This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis.. Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2.. Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

Topics: Adolescent; Adult; Allergens; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Cross-Over Studies; Double-Blind Method; Eye Diseases; Histamine H1 Antagonists, Non-Sedating; Humans; Middle Aged; Nasal Mucosa; Nose Diseases; Ophthalmic Solutions; Piperidines; Placebos; Rhinitis, Allergic, Seasonal; Terfenadine

Bilastine is a novel, nonsedating H(1)-antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR).. This randomized, double blind, placebo-controlled, parallel-group multicentre study evaluated the effect of 2 weeks' treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12-70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period.. Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis-associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%).. Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms.

Topics: Adolescent; Adult; Aged; Area Under Curve; Benzimidazoles; Child; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Loratadine; Male; Middle Aged; Piperidines; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome; Young Adult

Bilastine is a new non-sedative H(1) receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial).. To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR).. Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms.. The mean TSS-AUC(0-14 days) (score x day) was reduced in bilastine- and cetirizine-treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine-treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine-treated group (7.5% and 4.8%, respectively).. Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.

Topics: Adolescent; Adult; Aged; Benzimidazoles; Cetirizine; Child; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Receptors, Histamine H1; Rhinitis, Allergic, Seasonal; Time Factors

To model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H(1) receptor antagonist, from single- and multiple-dose studies in healthy adult subjects.. The pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.5, 5, 10, 20, 50, 100, 120, 160, 200 and 220 mg. In the multiple-dose studies, 127 healthy subjects received bilastine 10, 20, 40, 50, 80, 100, 140 or 200 mg/day as multiple doses during a 4-, 7- or 14-day period. The pharmacokinetic profile of bilastine was investigated using a simultaneous analysis of all concentration-time data by means of nonlinear mixed-effects modelling population pharmacokinetic software NONMEM version 6.1. Plasma concentrations were modelled according to a two-compartment open model with first-order absorption and elimination. For the pharmacodynamic analysis, the inhibitory effect of bilastine (inhibition of histamine-induced wheal and flare) was assessed on a preselected time schedule, and the predicted typical pharmacokinetic profile (based on the pharmacokinetic model previously developed) was used. An indirect response model was developed to describe the pharmacodynamic relationships between flare or wheal areas and bilastine plasma concentrations. Finally, once values of the concentration that produced 50% inhibition (IC(50)) had been estimated for wheal and flare effects, simulations were carried out to predict plasma concentrations for the doses of bilastine 5, 10 and 20 mg at steady state (72-96 hours).. A non-compartmental analysis resulted in linear kinetics of bilastine in the dose range studied. Bilastine was characterized by two-compartmental kinetics with a rapid-absorption phase (first-order absorption rate constant = 1.50 h(-1)), plasma peak concentrations were observed at 1 hour following administration and the maximal response was observed at approximately 4 hours or later. Concerning the selected pharmacodynamic model to fit the data (type I indirect response model), this selection is attributable to the presence of inhibitory bilastine plasma concentrations that decrease the input response function, i.e. the production of the skin reaction. This model resulted in the best fit of wheal and flare data. The estimates (with relative standard errors expressed in percentages in parentheses) of the apparent zero-order rate constant for flare or wheal spontaneous appearance (k(in)), the first-order rate constant for flare or wheal disappearance (k(out)) and bilastine IC(50) values were 0.44 ng/mL/h (14.60%), 1.09 h(-1) (15.14%) and 5.15 ng/mL (16.16%), respectively, for wheal inhibition, and 11.10 ng/mL/h (8.48%), 1.03 h(-1) (8.35%) and 1.25 ng/mL (14.56%), respectively, for flare inhibition. The simulation results revealed that bilastine plasma concentrations do not remain over the IC(50) value throughout the inter-dose period for doses of 5 and 10 mg. However, with a dose of 20 mg of bilastine administered every 24 hours, plasma concentrations remained over the IC(50) value during the considered period for the flare effect, and up to 20 hours for the wheal effect.. Pharmacokinetic and pharmacodynamic relationships of bilastine were reliably described with the use of an indirect response pharmacodynamic model; this led to an accurate prediction of the pharmacodynamic activity of bilastine.

Topics: Adult; Anti-Allergic Agents; Benzimidazoles; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine Antagonists; Humans; Male; Models, Biological; Piperidines; Single-Blind Method

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.

Topics: Administration, Oral; Adult; Affect; Attention; Benzimidazoles; Cross-Over Studies; Dermatitis, Contact; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine; Histamine H1 Antagonists; Humans; Hydroxyzine; Injections, Intradermal; Intradermal Tests; Male; Perception; Piperidines; Psychomotor Performance; Reaction Time; Reference Values; Young Adult

Allergic rhinitis and urticaria are extremely prevalent among all age groups. From the clinical experience, usually, an essential second-generation non-sedating H

Topics: Benzimidazoles; Histamine Antagonists; Humans; Pharmaceutical Preparations; Piperidines; Spectrometry, Fluorescence

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.

Topics: Acetates; Benzimidazoles; Chromatography, Thin Layer; Cyclopropanes; Humans; Piperidines; Quinolines; Research Design; Sulfides

Topics: Adolescent; Anemia; Benzimidazoles; Cyanosis; Exanthema; Humans; Male; Piperidines; Syndrome; Urticaria

Topics: Benzimidazoles; Cetirizine; Chronic Disease; Chronic Urticaria; Humans; India; Piperidines; Urticaria

Bilastine, a zwitterionic second-generation antihistamine containing a carboxyl group, has higher selectivity for H

Topics: Animals; Benzimidazoles; Cell Line; CHO Cells; Cricetulus; Entropy; Histamine H1 Antagonists, Non-Sedating; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Docking Simulation; Piperidines; Protein Binding; Receptors, Histamine H1; Static Electricity; Thermodynamics

This was an open-label, single-centre, phase I, bioavailability clinical trial. One drop of the bilastine ophthalmic formulation was administered once daily in each eye of the subjects for 5 days. Bilastine plasma concentrations were measured by HPLC-MS/MS. Adverse drug reactions were recorded for each subject during drug administration and follow-up visits.. Twelve healthy subjects (age 18-55 years) were included in the study. After multiple dose administration, bilastine reached a mean (± SD) maximum blood concentrations of 2682.26 ± 1615.88 pg/mL at a median time of 2.50 h (range 1.25-4.00 h). The half-life of bilastine in plasma was 7.88 ± 6.72 h. Steady state AUC was 19,512.51 ± 9248.76 h·pg/mL. Adverse events were mild and transient, consisting mainly of dysgeusia.. Bilastine once-daily ophthalmic formulation 6 mg/mL is absorbed into the bloodstream in low amounts by the ophthalmic route. The bilastine ophthalmic formulation showed a good safety profile after multiple dose administration.

Topics: Adolescent; Adult; Benzimidazoles; Histamine H1 Antagonists, Non-Sedating; Humans; Middle Aged; Piperidines; Tandem Mass Spectrometry; Urticaria; Young Adult

The objective of this study was to evaluate bilastine dosing recommendations in older adults and overcome the limitation of insufficient data from phase I studies in this underrepresented population. This was achieved by integrating bilastine physicochemical, in vitro and in vivo data in young adults and the effect of aging in the pharmacology by means of two alternative approaches: a physiologically-based pharmacokinetic (PBPK) model and a semi-mechanistic population pharmacokinetic (Senescence) model. Intestinal apical efflux and basolateral influx transporters were needed in the PBPK model to capture the observations from young adults after single i.v. (10 mg) and p.o. (20 mg) doses, supporting the hypothesis of involvement of gut transporters on secretion. The model was then used to extrapolate the pharmacokinetics (PKs) to elderly subjects considering their specific physiology. Additionally, the Senescence model was develop starting from a published population PK) model, previously applied for pediatrics, and incorporating declining functions on different physiological systems and changes in body composition with aging. Both models were qualified using observed data in a small group of young elderlies (N = 16, mean age = 68.69 years). The PBPK model was further used to evaluate the dose in older subjects (mean age = 80 years) via simulation. The PBPK model supported the hypothesis that basolateral influx and apical efflux transporters are involved in bilastine PK. Both, PBPK and Senescence models indicated that a 20 mg q.d. dose is safe and effective for geriatrics of any age. This approach provides an alternative to generate supplementary data to inform dosing recommendations in under-represented groups in clinical trials.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Benzimidazoles; Clinical Trials, Phase I as Topic; Computer Simulation; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Models, Biological; Piperidines; Young Adult

Concomitant montelukast and bilastine are used as additive therapy for seasonal allergic rhinoconjuctivitis and mild to moderate asthma. According to a literature review, no UV-visible spectrophotometric method has been reported yet for simultaneous estimation of montelukast sodium and bilastine in their combined pharmaceutical dosage forms.. Five different multicomponent spectrophotometric methods were therefore developed and validated for simultaneous estimation of montelukast sodium and bilastine using a risk assessment-based enhanced analytical quality-by-design approach.. The identification and assessment of method risk parameters were carried out using the risk priority number ranking and filtering method according to the International Conference on Harmonization (ICH) Q9 guideline. The wavelength for detection and solvents such as 0.1 N NaOH and 0.1 N HCl were found to be critical method parameters for the development of the target methods. The developed methods were validated as per the ICH Q2(R1) guideline.. The developed and validated methods were applied for assay of combined pharmaceutical dosage forms of montelukast sodium and bilastine and results were found to be in good agreement with their label claims.. The developed methods did not include the usage of any organic solvent and are a good alternative to the costly chromatography method. Hence, the methods are eco-friendly and economical for the simultaneous estimation of bilastine and montelukast sodium.. Five multicomponent spectrophotometric methods were developed for simultaneous estimation of montelukast sodium and bilastine using a risk-based analytical quality-by-design approach. An assay of combined tablet dosage forms of montelukast sodium and bilastine was then carried out using the developed methods.

Topics: Acetates; Benzimidazoles; Cyclopropanes; Piperidines; Quinolines; Risk Assessment; Sulfides

The Food and Drug Administration (FDA)'s guidelines and the Process Analytical Technology (PAT) approach conceptualize the idea of real time monitoring of a process, with the primary objective of improvement of quality and also of time and resources saving. New instruments are needed to perform an efficient PAT process control and Near Infrared Spectroscopy (NIRS), thanks to its rapid and drastic development of last years, could be a very good choice, in virtue of its high versatility, speed of analysis, non-destructiveness and absence of sample chemical treatment. This work was aimed to develop a NIR analytical method for bilastine assay in powder mixtures for direct compression. In particular, the use of NIR instrumentation should allow to control the bilastine concentration and the whole blending process, assuring the achievement of a homogeneous blend. The commercial tablet formulation of bilastine was particularly suitable for this purpose, due to its simple composition (four excipients) and direct compression manufacturing process. Calibration and validation set were prepared according to a Placket-Burman experimental design and acquired with a miniaturized NIR in-line instrument (MicroNIR by Viavi Solution Inc.). Chemometric was applied to optimize information extraction from spectra, by subjecting them to a Standard Normal Variate (SNV) and a Savitzky-Golay second derivative pre-treatment. This spectra pre-treatment, combined with the most suitable wavelength interval (resulted between 1087 and 1217 nm), enabled to obtain a Partial Least Square (PLS) model with a good predictive ability. The selected model, tried on laboratory and production batches, provided in both cases good assay predictions. Results were confirmed by traditional HPLC (High Performance Liquid Chromatography) API (Active Pharmaceutical Ingredient) content uniformity test on the final product.

Topics: Benzimidazoles; Calibration; Drug Compounding; Least-Squares Analysis; Piperidines; Powders; Research Design; Spectroscopy, Near-Infrared; Tablets; Technology, Pharmaceutical

Topics: Anti-Inflammatory Agents; Antiviral Agents; Benzimidazoles; Betacoronavirus; Betamethasone; Causality; Coronavirus Infections; COVID-19; Drug Eruptions; Drug Therapy, Combination; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Pandemics; Piperidines; Pneumonia, Viral; Prednisone; Ritonavir; SARS-CoV-2; Skin Diseases, Viral

A liquid chromatography (LC) stability-indicating method was developed and validated for the quantitative determination of bilastine in coated tablets.. The procedure was validated for specificity, linearity, robustness, precision, and accuracy. Plackett-Burmann experimental design was used to determine the robustness of the method.. Chromatographic separation was performed on a Shim-pack® RP-18 column with fluorescence detection. The degradation products formed under oxidative conditions were isolated and identified using high-resolution mass spectrometry (HRMS). In silico prediction of degradation products and in silico toxicity studies were also performed.. The LC method presented good recovery and precision (intraday and interday), the response was linear in a range of 0.20 to 0.70 μg mL-1, and the results demonstrated the robustness of the analytical method under the evaluated conditions.. The degradation products were identified as benzimidazole (DP1) and amine N-oxide of bilastine (DP2). The results for the toxicity studies demonstrated the high mutagenic potential of DP1 and hepatotoxicity and hERG I inhibitor effects of DP2.. Bilastine degradation products were identified as benzimidazole and amine N-oxide using HRMS.

Topics: Benzimidazoles; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Stability; Mass Spectrometry; Piperidines; Reproducibility of Results

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Benzimidazoles; Cyclopropanes; Humans; Piperidines; Quinolines; Seasons; Sulfides

Topics: Aged; Benzimidazoles; Eosinophilia; Histamine Antagonists; Humans; Male; Piperidines; Skin; Skin Diseases

Topics: Area Under Curve; Benzimidazoles; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Models, Biological; Piperidines; Urticaria

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.. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed.. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safety profile of bilastine 20 mg in patients aged ≥65 years with allergic rhinoconjunctivitis and/or urticaria.. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. The incidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88 (95% CI, 0.688-1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95% CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003-0.048) and 0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine.. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged ≥65 years. The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

Topics: Aged; Aged, 80 and over; Benzimidazoles; Conjunctivitis, Allergic; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Incidence; Male; Piperidines; Prospective Studies; Rhinitis, Allergic; Spain; Urticaria

Topics: Benzimidazoles; Chronic Disease; Humans; Piperidines; Treatment Outcome; Urticaria

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

Topics: Benzimidazoles; Diphenhydramine; HeLa Cells; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Receptors, Histamine H1; Terfenadine; Time Factors

Topics: Abdomen; Amoxicillin-Potassium Clavulanate Combination; Anti-Inflammatory Agents; Benzimidazoles; Carnitine; Clobetasol; Dermatitis; Edema; Erythema; Female; Humans; Injections, Subcutaneous; Keratosis; Lipolysis; Mesotherapy; Middle Aged; Peptides; Phosphatidylcholines; Piperidines; Prednisone; Subcutaneous Fat; Thigh

The aim of this study was to determine whether there were differences in health-related quality of life of patients with allergic rhinitis treated with bilastine 20 mg compared to those treated with loratadine 10 mg.. This was a prospective randomised double-blinded study.. Otolaryngology outpatient clinics in Criciúma, state of Santa Catarina, Brazil.. Seventy-three patients, aged between 18 and 63 years, of whom 36 were treated with loratadine 10 mg and 37 with bilastine 20 mg with medication administered once a day for 10 days.. The outcome was quality of life as assessed by the modified Rhinoconjunctivitis Quality of Life Questionnaire (RQLQm), which was applied at baseline and after 10 days of treatment.. The use of bilastine 20 mg or loratadine 10 mg significantly reduced RQLQm scores after 10 days of treatment (P < 0.001); however, there was no statistically significant difference between the two treatment groups (P > 0.05).. Health-related quality of life in patients with allergic rhinitis improved significantly after 10 days of treatment with loratadine and bilastine, and the effectiveness of both was equivalent.

Topics: Adolescent; Adult; Anti-Allergic Agents; Benzimidazoles; Brazil; Double-Blind Method; Female; Humans; Loratadine; Male; Middle Aged; Piperidines; Prospective Studies; Quality of Life; Rhinitis, Allergic; Treatment Outcome

Topics: Anti-Allergic Agents; Benzimidazoles; Chronic Disease; Drug Therapy, Combination; Female; Hepatitis B, Chronic; Humans; Middle Aged; Omalizumab; Piperidines; Prednisone; Urticaria; Viral Load; Viremia

This paper deals with the development of hydrophilic interaction liquid chromatographic (HILIC) method for the analysis of bilastine and its degradation impurities following Analytical Quality by Design approach. It is the first time that the method for bilastine and its impurities is proposed. The main objective was to identify the conditions where an adequate separation in minimal analysis duration could be achieved within a robust region. Critical process parameters which have the most influence on method performance were defined as acetonitrile content in the mobile phase, pH of the aqueous phase and ammonium acetate concentration in the aqueous phase. Box-Behnken design was applied for establishing a relationship between critical process parameters and critical quality attributes. The defined mathematical models and Monte Carlo simulations were used to identify the design space. Fractional factorial design was applied for experimental robustness testing and the method is validated to verify the adequacy of selected optimal conditions: the analytical column Luna(®) HILIC (100mm×4.6mm, 5μm particle size); mobile phase consisted of acetonitrile-aqueous phase (50mM ammonium acetate, pH adjusted to 5.3 with glacial acetic acid) (90.5:9.5, v/v); column temperature 30°C, mobile phase flow rate 1mLmin(-1), wavelength of detection 275nm.

Topics: Benzimidazoles; Chromatography, Liquid; Hydrophobic and Hydrophilic Interactions; Piperidines

Bilastine is a new oral selective, non-sedating histamine H1 antagonist for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. The European Medicines Agency requires an Environmental Risk Assessment (ERA) for all novel medicines for human use.. To calculate the bilastine predicted environmental concentration in surface water (PECsw; phase I ERA), and to determine the effects of bilastine on aquatic systems (phase II [tier A]).. Bilastine PECsw was calculated using the maximum daily dosage (20 mg), assuming that all administered bilastine was released into the aquatic environment. A persistence, bioaccumulation and toxicity assessment was conducted using the log Kow from the molecular structure. In phase II (tier A), a ready biodegradability test was performed, and bilastine's potential toxicity to various aquatic and sediment-dwelling micro-organisms was evaluated.. Bilastine PECSW was calculated as 0.1 μg L(-1), and the compound was not readily biodegradable. Bilastine had no significant effects on Chironomus riparius midges, or on the respiration rate of activated sludge. For green algae, the bilastine no observed effect concentration (NOEC) was 22 mg L(-1); bilastine had no effect on zebra fish development, or on the reproduction rate of daphnids.. Bilastine NOEC values against zebra fish, algae, daphnids, and aerobic organisms in activated sludge were at least 130 000-fold greater than the calculated PECSW value.. No environmental concerns exist from bilastine use in patients with allergic rhinoconjunctivitis or urticaria.

Topics: Animals; Benzimidazoles; Chironomidae; Chlorophyta; Daphnia; Environmental Monitoring; Female; Histamine H1 Antagonists, Non-Sedating; Male; No-Observed-Adverse-Effect Level; Piperidines; Risk Assessment; Sewage; Water Pollutants, Chemical; Zebrafish

Modern pharmacometrics can integrate and leverage all prior proprietary and public knowledge. Such methods can be used to scale across species or comparators, perform clinical trial simulation across alternative designs, confirm hypothesis and potentially reduce development burden, time and costs. Crucial yet typically lacking in integration is the pre-clinical stage. Prediction of PK in man, using in vitro and in vivo studies in different animal species, is increasingly well theorized but could still find wider application in drug development. The aim of the present work was to explore methods for bridging pharmacokinetic knowledge from animal species (i.v. and p.o.) and man (p.o.) into i.v. in man using the antihistamine drug bilastine as example. A model, predictive of i.v. PK in man, was developed on data from two pre-clinical species (rat and dog) and p.o. in man bilastine trials performed earlier. In the knowledge application stage, two different approaches were used to predict human plasma concentration after i.v. of bilastine: allometry (several scaling methods) and a semi-physiological method. Both approaches led to successful predictions of key i.v. PK parameters of bilastine in man. The predictive i.v. PK model was validated using later data from a clinical study of i.v. bilastine. Introduction of such knowledge in development permits proper leveraging of all emergent knowledge as well as quantification-based exploration of PK scenario, e.g. in special populations (pediatrics, renal insufficiency, comedication). In addition, the methods permit reduction or elimination and certainly optimization of learning trials, particularly those concerning alternative off-label administration routes.

Topics: Administration, Intravenous; Administration, Oral; Animals; Benzimidazoles; Dogs; Female; Histamine Antagonists; Humans; Knowledge Bases; Male; Models, Animal; Models, Biological; Piperidines; Rats; Rats, Wistar; Reproducibility of Results; Species Specificity

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

Topics: Administration, Oral; Benzimidazoles; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

The most commonly occurring allergic diseases can involve a daytime drowsiness associated with the condition itself. The antihistamines used in their treatment can also have central effects and affect certain occupations concerned with risk, road safety and maritime and air navigation. Cognitive tests, experimental studies and epidemiological data recommend avoiding 1st generation antihistamines for people who must drive regularly and/or professions concerned with safety. Although there are no comparative studies on real driving between 1st and 2nd generation antihistamines, in this type of patients there should be a preference for prescribing those with least possible central effect, especially those which are a good substrate for transmembrane transporter pumps such as P-glycoprotein and therefore have a low capacity for crossing the hematoencephalic barrier, thus allowing a broader window for therapy. In this sense, bilastine is a good P-glycoprotein substrate and shows good tolerance at CNS level, in both psychometric trials and real driving test protocols, even at double the dose recommended in the technical file.

Topics: Aircraft; Automobile Driving; Benzimidazoles; Cognition; Histamine H1 Antagonists; Humans; Occupations; Piperidines; Psychomotor Performance; Risk

This study evaluated the tissue distribution of total radioactivity in male albino, male pigmented, and time-mated female albino rats after oral administration of a single dose of [¹⁴C]-bilastine (20 mg/kg). Although only 1 animal was analyzed at each time point, there were apparent differences in bilastine distribution. Radioactivity was distributed to only a few tissues at low levels in male rats, whereas distribution was more extensive and at higher levels in female rats. This may be a simple sex-related difference. In each group and at each time point, concentrations of radioactivity were high in the liver and kidney, reflecting the role of these organs in the elimination process. In male albino rats, no radioactivity was measurable by 72 hours postdose. In male pigmented rats, only the eye and uveal tract had measurable levels of radioactivity at 24 hours. Measureable levels of radioactivity were retained in these tissues at the final sampling time point (336 hours postdose), indicating a degree of melanin-associated binding. In time-mated female rats, but not in albino or pigmented male rats, there was evidence of low-level passage of radioactivity across the placental barrier into fetal tissues as well as low-level transfer of radioactivity into the brain.

Topics: Animals; Autoradiography; Benzimidazoles; Eye; Female; Histamine H1 Antagonists, Non-Sedating; Kidney; Liver; Male; Maternal-Fetal Exchange; Melanins; Pigmentation; Piperidines; Pregnancy; Radioactive Tracers; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Sex Characteristics; Tissue Distribution; Whole Body Imaging

Membrane transporters play a significant role in facilitating transmembrane drug movement. For new pharmacological agents, it is important to evaluate potential interactions (e.g., substrate specificity and/or inhibition) with human transporters that may affect their pharmacokinetics, efficacy, or toxicity. Bilastine is a new nonsedating H₁ antihistamine indicated for the treatment of allergic rhinoconjunctivitis and urticaria. The in vitro inhibitory effects of bilastine were assessed on 12 human transporters: four efflux [multidrug resistance protein 1 (MDR1) or P-glycoprotein, breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2), and bile salt export pump) and eight uptake transporters (sodium taurocholate cotransporting polypeptide, organic cation transporter (OCT)1, organic anion transporter (OAT)1, OAT3, OCT2, OATP2B1, OATP1B1, and OATP1B3). Only mild inhibition was found for MDR1-, OCT1-, and OATP2B1-mediated transport of probe substrates at the highest bilastine concentration assayed (300 μM; half-maximal inhibitory concentration: ≥300 μM). Bilastine transport by MDR1, BCRP, OAT1, OAT3, and OCT2 was also investigated in vitro. Only MDR1 active transport of bilastine was relevant, whereas it did not appear to be a substrate of OCT2, OAT1, or OAT3, nor was it transported substantially by BCRP. Drug-drug interactions resulting from bilastine inhibition of drug transporters that would be generally regarded as clinically relevant are unlikely. Additionally, bilastine did not appear to be a substrate of human BCRP, OAT1, OAT3, or OCT2 and thus is not a potential victim of inhibitors of these transporters. On the other hand, based on in vitro evaluation, clinically relevant interactions with MDR1 inhibitors are anticipated.

Topics: Animals; ATP-Binding Cassette Transporters; Benzimidazoles; Biological Transport; Caco-2 Cells; Cell Line; Cell-Free System; CHO Cells; Cricetinae; Cricetulus; Dogs; Drug Evaluation, Preclinical; Histamine H1 Antagonists, Non-Sedating; Humans; Membrane Transport Modulators; Organic Anion Transporters; Osmolar Concentration; Piperidines; Protein Isoforms; Recombinant Proteins; Spodoptera

Topics: Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists; Humans; Piperidines

Topics: Benzimidazoles; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

We set out to establish the in vivo histamine H(1) receptor antagonistic (antihistaminic) and antiallergic properties of bilastine.. 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 the in vivo antihistaminic activity experiments, bilastine was shown to have a positive effect, similar to that of cetirizine and more potent than that of fexofenadine. The results of the in vivo antiallergic activity experiments showed that the properties of bilastine in this setting are similar to those observed for cetirizine and superior to fexofenadine in the model of passive cutaneous anaphylactic reaction. When active cutaneous anaphylactic reaction experiments were conducted, bilastine showed significant activity, less potent than that observed with cetirizine but superior to that of fexofenadine. Evaluation of the type III allergic reaction showed that of the antihistamines only bilastine was able to inhibit oedema in sensitised mice, although its effect in this respect was much less potent than that observed with dexamethasone. In terms of the type IV allergic reaction, neither bilastine, cetirizine nor fexofenadine significantly modified the effect caused by oxazolone.. The results of our in vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastine possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

Topics: Animals; Benzimidazoles; Bradykinin; Bronchial Spasm; Capillary Permeability; Cetirizine; Dermatitis; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Histamine Antagonists; Hypersensitivity; Male; Mice; Molecular Structure; Oxazolone; Piperidines; Rats; Rats, Wistar; Receptors, Histamine H1; Serotonin; Structure-Activity Relationship; Terfenadine; Time Factors

This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist.. 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. Receptor selectivity was established using a receptor binding screening panel and a receptor antagonism screening conducted in guinea-pig, rat and rabbit tissues. Inhibition of inflammatory mediators was determined through the Schultz-Dale reaction in sensitised guinea-pig ileum.. Bilastine binds to histamine H1-receptors as indicated by its displacement of [3H]-pyrilamine from H1-receptors expressed in guinea-pig cerebellum and human embryonic kidney (HEK) cell lines. The studies conducted on guinea-pig smooth muscle demonstrated the capability of bilastine to antagonise H1-receptors. Bilastine is selective for histamine H1-receptors as shown in receptor-binding screening conducted to determine the binding capacity of bilastine to 30 different receptors. The specificity of its H1-receptor antagonistic activity was also demonstrated in a series of in vitro experiments conducted on guinea-pig and rat tissues. The results of these studies confirmed the lack of significant antagonism against serotonin, bradykinin, leukotriene D4, calcium, muscarinic M3-receptors, alpha1-adrenoceptors, beta2-adrenoceptors, and H2- and H3-receptors. The results of the in vitro Schultz-Dale reaction demonstrated that bilastine also has anti-inflammatory activity.. These preclinical studies provide evidence that bilastine has H1- antihistamine activity, with high specificity for H1-receptors, and poor or no affinity for other receptors. Bilastine has also been shown to have anti-inflammatory properties.

Topics: Animals; Benzimidazoles; Binding, Competitive; Cell Line; Drug Evaluation, Preclinical; Guinea Pigs; Histamine H1 Antagonists; Humans; In Vitro Techniques; Male; Organ Specificity; Piperidines; Protein Binding; Rabbits; Rats; Receptors, Histamine H1

A matrix solid-phase dispersion (MSPD) procedure for the isolation and HPLC determination of a new antiallergic agent, bilastine, in rat faeces is presented. The effect on recovery of empirical variables such as nature, pH and volume of the washing and elution liquids and nature of the adsorbent has been tested. The best recoveries were attained using an octadecylsilyl sorbent, 10 ml of a 0.1 M NaHCO3-Na2CO3 aqueous buffer of pH 10.0 as washing solvent and 10 ml of methanol as elution solvent. The extracts were evaporated to dryness and reconstituted in mobile phase before their injection into a HPLC system, equipped with a Discovery RP-amide C16 column and a fluorescence detector. The method allows one to reach recoveries of 95.0% within the concentration range 0.05-10 microg/g, with within-day repeatabilities of less than 5% and between-day repeatabilities of less than 9% within this range. This method has been successfully applied to the excretion studies of bilastine in the rat.

Topics: Animals; Anti-Allergic Agents; Benzimidazoles; Chromatography, High Pressure Liquid; Feces; Piperidines; Rats; Reference Standards; Reproducibility of Results; Spectrometry, Fluorescence