Sinha Ekta, Bhagat Sagar, Patil Saiprasad, Kodgule Rahul, Modi Vinayak, Barkate Hanmant
Glenmark Pharmaceuticals Ltd, Mumbai, Maharashtra, 400099, India.
Glenmark Pharmaceuticals Ltd, Navi Mumbai, Maharashtra, 400709, India.
Eur J Drug Metab Pharmacokinet. 2025 Jul;50(4):319-325. doi: 10.1007/s13318-025-00946-3. Epub 2025 May 27.
Antihistamines are an essential treatment option for cough and upper respiratory symptoms. Bilastine is a 2nd-generation antihistamine which is approved as a 20 mg once daily dose. The objective of the current study is to compare the oral bioavailability of bilastine administered thrice daily as a triple combination syrup of test product bilastine + dextromethorphan hydrobromide + phenylephrine hydrochloride (3.3 mg + 10 mg + 5 mg)/5 mL and a reference product of single-dose administration of 2.5 mg/mL (bilastine 2.5 mg) in healthy, adult, male human subjects under fed condition.
This was an open-label, balanced, randomized, two-treatment, two-period, cross-over comparative bioavailability study. Patients were administered 10 mL of three 8-hourly doses of the triple combination test product and once daily dose of the reference product (syrup containing bilastine 2.5 mg). A 7-day washout period was implemented between doses. Blood samples were collected to assess the oral bioavailability of the test and reference products. Each subject received both treatments, serving as their own control, eliminating the need for a separate control group. Blood samples were collected pre-dose and at various intervals post-dose to determine plasma concentrations of bilastine using LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry. Primary pharmacokinetic parameters were analyzed for bioequivalence using SAS version 9.4.
A total of 34 subjects out of 36 enrolled, successfully completed the study, and were analyzed. The geometric mean ratios of test versus reference product for the areas under the curve (AUC and AUC ) were 88.42% (84.15-92.91%) and 98.06% (93.63-102.69%), respectively, which are within the bioequivalence acceptance limits of 80.00-125.00%.
Our study concluded that the test product, bilastine + dextromethorphan hydrobromide + phenylephrine hydrochloride syrup (3.3 mg + 10 mg + 5 mg)/5 mL, and the reference product, bilastine solution 2.5 mg/mL, are bioequivalent with respect to the extent of absorption and were well tolerated.
抗组胺药是治疗咳嗽和上呼吸道症状的重要选择。比拉斯汀是一种第二代抗组胺药，已获批每日一次20毫克的剂量。本研究的目的是比较在进食条件下，健康成年男性受试者中，比拉斯汀与氢溴酸右美沙芬 + 盐酸去氧肾上腺素以（3.3毫克 + 10毫克 + 5毫克）/5毫升的比例制成的三联糖浆每日三次给药时的口服生物利用度，以及单剂量2.5毫克/毫升（比拉斯汀2.5毫克）的参比制剂的口服生物利用度。
这是一项开放标签、平衡、随机、双治疗、双周期、交叉对照的生物利用度比较研究。患者分别接受10毫升的三联试验制剂，每8小时一次，共三次，以及参比制剂（含2.5毫克比拉斯汀的糖浆）每日一次。两次给药之间有7天的洗脱期。采集血样以评估试验制剂和参比制剂的口服生物利用度。每个受试者接受两种治疗，自身作为对照，无需单独设立对照组。给药前和给药后不同时间点采集血样，使用液相色谱 - 质谱/质谱联用仪（LC - MS/MS）测定比拉斯汀的血浆浓度。使用SAS 9.4版本分析主要药代动力学参数的生物等效性。
36名受试者中共有34名成功完成研究并纳入分析。试验制剂与参比制剂的曲线下面积（AUC和AUC ）的几何平均比值分别为88.42%（84.15 - 92.91%）和98.06%（93.63 - 102.69%），均在生物等效性接受限度80.00 - 125.00%之内。
我们的研究得出结论，试验制剂比拉斯汀 + 氢溴酸右美沙芬 + 盐酸去氧肾上腺素糖浆（3.3毫克 + 10毫克 + 5毫克）/5毫升与参比制剂2.5毫克/毫升比拉斯汀溶液在吸收程度方面具有生物等效性，且耐受性良好。
