Centre d'Investigació de Medicaments (CIM), Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Clinical Epidemiology and Public Health Department, Hospital de la Santa Creu i Santa Pau, Barcelona, Spain, Universitat Autónoma de Barcelona (UAB), Bellaterra, Spain.
Eur J Pharm Sci. 2024 Dec 1;203:106900. doi: 10.1016/j.ejps.2024.106900. Epub 2024 Sep 10.
Bilastine is a well-known non-sedating second-generation antihistamine authorised worldwide for the symptomatic treatment of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria with proven efficacy and good safety and tolerability profile. When the oral route is not suitable or a rapid onset of action is preferred, parenteral formulations represent an effective treatment option. However, the parenteral formulations currently available are sedating antihistamines. The objective of this research was to compare the peripheral anti-H activity of different bilastine formulations (i.v., i.m. and oral) and dexchlorpheniramine among them also versus placebo.
This was a single-dose, randomized, crossover, double-blind, placebo-controlled, phase I clinical study performed on 25 adult healthy volunteers that compared the peripheral antihistaminic activity of a single dose of bilastine 12 mg i.v., bilastine 12 mg i.m., bilastine 20 mg oral tablets and dexchlorpheniramine 5 mg i.m. among them and versus placebo by inhibiting the histamine-induced wheal and flare (W&F) response. Pharmacokinetics, safety, and tolerability were also evaluated.
All bilastine formulations showed a rapid onset of action (15 min for parenteral and 30 min for the oral formulation), and the maximum effect in both wheal (i.v. 74.44 %; i.m.:74.29 %; oral 70,27 %) and flare area reduction (i.v. and i.m. 80.63 %; oral 77.67 %), was significantly larger compared to dexchlorpheniramine i.m. (25.85 % for wheal and 28.65 % for flare) and placebo (1.35 % for wheal and 4.02 % for flare). A more pronounced reduction in itching score was reached for bilastine oral, followed by i.m. and i.v. formulations. No serious adverse events (SAEs) were reported during the study, and 8 treatment-emergent adverse events (TEAEs) were reported by 5 subjects, all resolved without sequelae. For psychomotor assessments, dexchlorpheniramine i.m. showed a fast onset of drowsiness, as well as decreased attention and coordination when compared to all bilastine formulations and placebo.
All bilastine formulations showed a peripheral H-blocking effect inducing a significantly greater inhibition of the wheal and flare response as compared to dexchlorpheniramine i.m. or placebo and provided a greater reduction of the itching sensation score. This study reconfirmed that bilastine has no sedative effect, even in a parenteral formulation. These results suggest that new bilastine parenteral formulation (i.v. or i.m.) may represent a suitable alternative for patients requiring immediate treatment of histamine-mediated type I hypersensitivity reactions, such as acute urticaria, or in those cases where oral administration is not possible.
比拉斯汀是一种广为人知的非镇静第二代抗组胺药，已在全球范围内获得批准，用于治疗过敏性鼻炎（季节性和常年性）和荨麻疹，具有良好的疗效和安全性及耐受性。当口服途径不合适或需要快速起效时，注射制剂是一种有效的治疗选择。然而，目前可用的注射制剂是镇静性抗组胺药。本研究的目的是比较不同比拉斯汀制剂（静脉、肌肉和口服）与右旋氯苯那敏的外周抗-H 活性，其中还包括与安慰剂的比较。
这是一项单剂量、随机、交叉、双盲、安慰剂对照的 I 期临床试验，在 25 名成年健康志愿者中进行，比较了单次静脉注射比拉斯汀 12mg、肌肉注射比拉斯汀 12mg、口服比拉斯汀 20mg 片剂和肌肉注射右旋氯苯那敏 5mg 的外周抗组胺活性，并与安慰剂进行了比较，通过抑制组胺诱导的风团和红斑（W&F）反应来评估药代动力学、安全性和耐受性。
所有比拉斯汀制剂均显示出快速起效（静脉注射 15 分钟，口服 30 分钟），在风团（静脉注射 74.44%；肌肉注射 74.29%；口服 70.27%）和红斑面积减少方面的最大效应（静脉注射和肌肉注射 80.63%；口服 77.67%）均明显大于右旋氯苯那敏肌肉注射（风团 25.85%，红斑 28.65%）和安慰剂（风团 1.35%，红斑 4.02%）。口服比拉斯汀的瘙痒评分降低更为明显，其次是肌肉注射和静脉注射制剂。研究期间未报告严重不良事件（SAE），5 名受试者报告了 8 例治疗后出现的不良事件（TEAE），均无后遗症。对于精神运动评估，与所有比拉斯汀制剂和安慰剂相比，右旋氯苯那敏肌肉注射会迅速引起嗜睡，并降低注意力和协调性。
所有比拉斯汀制剂均显示出外周 H 阻断作用，与右旋氯苯那敏肌肉注射或安慰剂相比，能显著抑制风团和红斑反应，瘙痒评分降低更为明显。这项研究再次证实，比拉斯汀没有镇静作用，即使是在注射制剂中。这些结果表明，新的比拉斯汀注射制剂（静脉或肌肉注射）可能是需要立即治疗组胺介导的 I 型过敏反应（如急性荨麻疹）的患者或无法口服的患者的一种合适的替代选择。
